daniel-scalioni/Supervisionado · Datasets at Hugging Face

entities listlengths 0 637	sentence stringlengths 1 68k
[]	The splice - site mutation would lead to skipping of exon 3 , accompanied by a frameshift , and thus would produce aberrant ASPA .
[ { "name": "Canavan", "pos": [ 21, 28 ], "type": "Disease" } ]	Of the 128 unrelated Canavan chromosomes analyzed , 88 were from probands of Ashkenazi Jewish descent .
[]	The glu285 - - > ala mutation was predominant ( 82 . 9 % ) in this population , followed by the tyr231 - - > ter ( 14 . 8 % ) and 433 - - 2 ( A - - > G ) ( 1 . 1 % ) mutations .
[]	The three mutations account for 98 .
[ { "name": "Canavan", "pos": [ 11, 18 ], "type": "Disease" } ]	8 % of the Canavan chromosomes of Ashkenazi Jewish origin .
[]	The ala305 - - > glu mutation was found exclusively in non - Jewish probands of European descent and constituted 60 % of the 40 mutant chromosomes .
[ { "name": "Canavan disease", "pos": [ 98, 113 ], "type": "Disease" } ]	Predominant occurrence of certain mutations among Ashkenazi Jewish and non - Jewish patients with Canavan disease would suggest a founding - father effect in propagation of these mutant chromosomes
[ { "name": "myotonic dystrophy", "pos": [ 33, 51 ], "type": "Disease" } ]	Intelligence quotient profile in myotonic dystrophy , intergenerational deficit , and correlation with CTG amplification .
[ { "name": "myotonic dystrophy", "pos": [ 155, 173 ], "type": "Disease" }, { "name": "DM", "pos": [ 176, 178 ], "type": "Disease" }, { "name": "DM", "pos": [ 268, 270 ], "type": "Disease" } ]	An abbreviated Wechsler Adult Intelligence Scale Revised ( WAIS - R ) was used to assess verbal and arithmetical cognitive performance in 55 subjects with myotonic dystrophy ( DM ) , covering all grades of disease severity , and 31 controls at 50 % risk of inheriting DM .
[]	Scaled scores from the assessment were converted into an intelligence quotient ( IQ ) estimation on each person .
[ { "name": "DM", "pos": [ 59, 61 ], "type": "Disease" } ]	Significant IQ differences were found between ( 1 ) all 55 DM subjects ( mean 90 . 2 , SD 16 . 1 ) and 31 controls ( 102 . 6 , SD 9 . 4 ) , with no sex differences in either group ; ( 2 ) 15 affected parents ( 99 . 3 , SD 12 . 2 ) and their affected children ( 88 . 1 , SD 17 . 2 ) , where significance was dependent on parental sex being female ; and ( 3 ) 15 pairs of affected sibs ( 89 . 6 , SD 13 . 2 ) and their normal sibs ( 100 . 2 , SD 7 . 6 ) .
[]	IQ steadily declined as ( 1 ) the age of onset of signs and symptoms decreased , and ( 2 ) the CTG expansion size increased .
[]	The correlation appeared to be more linear with age of onset .
[ { "name": "DM", "pos": [ 74, 76 ], "type": "Disease" } ]	The correlation of IQ difference and CTG expansion difference in both the DM parent - child pairs and normal sib - affected sib pairs was poor , indicating that CTG expansion is not a reliable predictor of IQ either in individual persons or families .
[ { "name": "DM", "pos": [ 42, 44 ], "type": "Disease" } ]	Further analysis of cognitive function in DM is required to clarify specific deficits characteristic of this patient group
[ { "name": "Adenomatous polyposis coli", "pos": [ 0, 26 ], "type": "Disease" } ]	Adenomatous polyposis coli and a cytogenetic deletion of chromosome 5 resulting from a maternal intrachromosomal insertion .
[ { "name": "autism", "pos": [ 110, 116 ], "type": "Disease" } ]	We present the clinical and laboratory findings in an institutionalised adult patient originally referred for autism .
[ { "name": "colorectal cancer", "pos": [ 15, 32 ], "type": "Disease" }, { "name": "APC", "pos": [ 198, 201 ], "type": "Disease" } ]	A high risk of colorectal cancer was predicted when an interstitial deletion of the long arm of chromosome 5 , del ( 5 ) ( q15q22 . 3 ) , was detected in her lymphocytes and deletion of the MCC and APC genes confirmed by molecular analysis .
[ { "name": "Adenomatous polyposis coli", "pos": [ 0, 26 ], "type": "Disease" }, { "name": "carcinoma of the rectum", "pos": [ 31, 54 ], "type": "Disease" } ]	Adenomatous polyposis coli and carcinoma of the rectum were subsequently diagnosed in the patient .
[ { "name": "mentally retarded", "pos": [ 19, 36 ], "type": "Disease" }, { "name": "autistic", "pos": [ 39, 47 ], "type": "Disease" }, { "name": "dysmorphic features", "pos": [ 64, 83 ], "type": "Disease" } ]	She was profoundly mentally retarded , autistic , and had minor dysmorphic features consistent with those of previous patients with similar deletions .
[]	The deletion arose as a result of recombination within the small insertion loop formed at meiosis by the direct insertion ( dir ins ( 5 ) ( q22 . 3q14 . 2q15 ) ) found in the patients mother .
[ { "name": "APC", "pos": [ 69, 72 ], "type": "Disease" } ]	This family further confirms the cytogenetic mapping of both MCC and APC genes to 5q22 and comparison with other recent cases suggests that both genes and their closely linked markers lie within the 5q22 .
[]	1 subband
[ { "name": "Familial male breast cancer", "pos": [ 0, 27 ], "type": "Disease" } ]	Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q .
[ { "name": "Breast cancer", "pos": [ 0, 13 ], "type": "Disease" } ]	Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis .
[ { "name": "male breast cancer", "pos": [ 55, 73 ], "type": "Disease" }, { "name": "hereditary breast and ovarian cancer", "pos": [ 93, 129 ], "type": "Disease" } ]	We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus , BRCA1 , on chromosome 17q .
[]	We found strong evidence against linkage to BRCA1 ( lod score - 16 . 63 ) and the best estimate of the proportion of linked families was 0 % ( 95 % CI 0 - 18 % ) .
[ { "name": "breast cancer", "pos": [ 100, 113 ], "type": "Disease" }, { "name": "male breast cancer", "pos": [ 158, 176 ], "type": "Disease" } ]	Our results indicate that there is a gene ( s ) other than BRCA1 which predisposes to early - onset breast cancer in women and which confers a higher risk of male breast cancer .
[ { "name": "male breast cancer", "pos": [ 61, 79 ], "type": "Disease" } ]	Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene .
[ { "name": "Ewing family of tumors", "pos": [ 27, 49 ], "type": "Disease" }, { "name": "malignant melanoma of soft parts", "pos": [ 52, 84 ], "type": "Disease" }, { "name": "desmoplastic small round cell tumors", "pos": [ 89, 125 ], "type": "Disease" } ]	The EWS gene , involved in Ewing family of tumors , malignant melanoma of soft parts and desmoplastic small round cell tumors , codes for an RNA binding protein with novel regulatory domains .
[ { "name": "solid tumors", "pos": [ 102, 114 ], "type": "Disease" }, { "name": "Ewing sarcoma", "pos": [ 125, 138 ], "type": "Disease" }, { "name": "neuroectodermal tumors", "pos": [ 159, 181 ], "type": "Disease" }, { "name": "malignant melanoma of soft parts", "pos": [ 184, 216 ], "type": "Disease" }, { "name": "desmoplastic small round cell tumors", "pos": [ 221, 257 ], "type": "Disease" } ]	The EWS gene , which maps to band q12 of human chromosome 22 , is involved in a wide variety of human solid tumors including Ewing sarcoma , related primitive neuroectodermal tumors , malignant melanoma of soft parts and desmoplastic small round cell tumors .
[ { "name": "tumors", "pos": [ 9, 15 ], "type": "Disease" } ]	In these tumors , the EWS is fused to genes encoding transcriptional activators / repressors , like Fli - 1 or erg or ATF 1 or wt1 .
[]	To better understand the function of the EWS protein , we cloned the EWS cDNA .
[]	Sequence analysis of this cDNA revealed differential splicing involving two exons encoding 72 amino acids .
[]	Both alternatively spliced transcripts , EWS and EWS - b , are expressed in a variety of cells .
[]	Because EWS proteins contain putative conserved RNA binding motifs , we studied the RNA binding properties of the EWS protein .
[]	The EWS - b protein binds to RNA in vitro and , specifically , to poly G and poly U .
[]	The RNA binding activity was localized to the carboxy terminal 86 amino acids , which constitute RGG box .
[]	Thus the amino terminal domain of EWS ( NTD - EWS ) , which is involved in chromosome translocation may regulate the specificity of RNA binding activity of EWS .
[ { "name": "Ewings sarcoma", "pos": [ 50, 64 ], "type": "Disease" } ]	An EWS - erg chimeric protein , which is found in Ewings sarcoma cells , functions as a transcriptional activator .
[]	Mutational analysis of EWS - erg chimeric protein revealed that NTD - EWS functions as a regulatory domain for the transcriptional activation properties of EWS - erg chimeric protein . .
[ { "name": "Canavan disease", "pos": [ 0, 15 ], "type": "Disease" } ]	Canavan disease : genomic organization and localization of human ASPA to 17p13 - ter and conservation of the ASPA gene during evolution .
[ { "name": "Canavan disease", "pos": [ 0, 15 ], "type": "Disease" }, { "name": "spongy degeneration of the brain", "pos": [ 21, 53 ], "type": "Disease" }, { "name": "leukodystrophy", "pos": [ 68, 82 ], "type": "Disease" }, { "name": "deficiency of aspartoacylase", "pos": [ 97, 125 ], "type": "Disease" } ]	Canavan disease , or spongy degeneration of the brain , is a severe leukodystrophy caused by the deficiency of aspartoacylase ( ASPA ) .
[ { "name": "Canavan disease", "pos": [ 95, 110 ], "type": "Disease" } ]	Recently , a missense mutation was identified in human ASPA coding sequence from patients with Canavan disease .
[]	The human ASPA gene has been cloned and found to span 29 kb of the genome .
[]	Human aspartoacylase is coded by six exons intervened by five introns .
[]	The exons vary from 94 ( exon III ) to 514 ( exon VI ) bases .
[]	The exon / intron splice junction sites follow the gt / ag consensus sequence rule .
[]	Southern blot analysis of genomic DNA from human / mouse somatic cell hybrid cell lines localized ASPA to human chromosome 17 .
[]	The human ASPA locus was further mapped in the 17p13 - ter region by fluorescence in situ hybridization .
[]	The bovine aspa gene has also been cloned , and its exon / intron organization is identical to that of the human gene .
[]	The 500 - base sequence upstream of the initiator ATG codon in the human gene and that in the bovine gene are 77 % identical .
[]	Human ASPA coding sequences cross - hybridize with genomic DNA from yeast , chicken , rabbit , cow , dog , mouse , rat , and monkey .
[]	The specificity of cross - species hybridization of coding sequences suggests that aspartoacylase has been conserved during evolution .
[ { "name": "Canavan disease", "pos": [ 96, 111 ], "type": "Disease" } ]	It should now be possible to identify mutations in the noncoding genomic sequences that lead to Canavan disease and to study the regulation of ASPA . .
[ { "name": "Myotonic dystrophy", "pos": [ 0, 18 ], "type": "Disease" } ]	Myotonic dystrophy : size - and sex - dependent dynamics of CTG meiotic instability , and somatic mosaicism .
[ { "name": "Myotonic dystrophy", "pos": [ 0, 18 ], "type": "Disease" }, { "name": "DM", "pos": [ 21, 23 ], "type": "Disease" }, { "name": "neuromuscular disorder", "pos": [ 43, 65 ], "type": "Disease" }, { "name": "DM", "pos": [ 175, 177 ], "type": "Disease" } ]	Myotonic dystrophy ( DM ) is a progressive neuromuscular disorder which results from elongations of an unstable ( CTG ) n repeat , located in the 3 untranslated region of the DM gene .
[]	A correlation has been demonstrated between the increase in the repeat number of this sequence and the severity of the disease .
[]	However , the clinical status of patients cannot be unambiguously ascertained solely on the basis of the number of CTG repeats .
[]	Moreover , the exclusive maternal inheritance of the congenital form remains unexplained .
[ { "name": "DM", "pos": [ 56, 58 ], "type": "Disease" } ]	Our observation of differently sized repeats in various DM tissues from the same individual may explain why the size of the mutation observed in lymphocytes does not necessarily correlate with the severity and nature of symptoms .
[ { "name": "DM", "pos": [ 68, 70 ], "type": "Disease" } ]	Through a molecular and genetic study of 142 families including 418 DM patients , we have investigated the dynamics of the CTG repeat meiotic instability .
[]	A positive correlation between the size of the repeat and the intergenerational enlargement was observed similarly through male and female meioses for < or = 0 .
[]	5 - kb CTG sequences .
[]	Beyond 0 .
[]	5 kb , the intergenerational variation was more important through female meioses , whereas a tendency to compression was observed almost exclusively in male meioses , for > or = 1 .
[]	5 - kb fragments .
[]	This implies a size - and sex - dependent meiotic instability .
[]	Moreover , segregation analysis supports the hypothesis of a maternal as well as a familial predisposition for the occurrence of the congenital form .
[]	Finally , this analysis reveals a significant excess of transmitting grandfathers partially accounted for by increased fertility in affected males
[ { "name": "phenylketonuria", "pos": [ 115, 130 ], "type": "Disease" } ]	Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria .
[ { "name": "hyperphenylalaninemic", "pos": [ 153, 174 ], "type": "Disease" } ]	Taking advantage of the illegitimate transcription of the phenylalanine hydroxylase ( PAH ) gene , we have been able to analyse the PAH cDNA sequence of hyperphenylalaninemic children in circulating lymphocytes .
[]	Using this approach , we have also identified 3 novel mutations in cDNA from liver and lymphocytes of two patients .
[]	One mutation , detected by the abnormal pattern of migration of an amplified fragment , is a C to T transition in the splice acceptor site of intron 10 , which resulted in the skipping of exon 11 with the premature termination of RNA translation downstream from exon 12 ( - 3 IVS10 ) .
[]	The other two mutations are missense mutations in exons 10 and 11 ( respectively , L333F and E390G ) .
[ { "name": "phenylketonuria", "pos": [ 242, 257 ], "type": "Disease" } ]	The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria . .
[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 66, 111 ], "type": "Disease" } ]	High residual arylsulfatase A ( ARSA ) activity in a patient with late - infantile metachromatic leukodystrophy .
[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 39, 84 ], "type": "Disease" }, { "name": "MLD", "pos": [ 87, 90 ], "type": "Disease" } ]	We identified a patient suffering from late - infantile metachromatic leukodystrophy ( MLD ) who has a residual arylsulfatase A ( ARSA ) activity of about 10 % .
[ { "name": "adult MLD", "pos": [ 93, 102 ], "type": "Disease" } ]	Fibroblasts of the patient show significant sulfatide degradation activity exceeding that of adult MLD patients .
[]	Analysis of the ARSA gene in this patient revealed heterozygosity for two new mutant alleles in one allele , deletion of C 447 in exon 2 leads to a frameshift and to a premature stop codon at amino acid position 105 ; in the second allele , a G - - > A transition in exon 5 causes a Gly309 - - > Ser substitution .
[]	Transient expression of the mutant Ser309 - ARSA resulted in only 13 % enzyme activity of that observed in cells expressing normal ARSA .
[]	The mutant ARSA is correctly targeted to the lysosomes but is unstable .
[ { "name": "late - infantile type of MLD", "pos": [ 68, 96 ], "type": "Disease" } ]	These findings are in contrast to previous results showing that the late - infantile type of MLD is always associated with the complete absence of ARSA activity .
[]	The expression of the mutant ARSA protein may be influenced by particular features of oligodendrocytes , such that the level of mutant enzyme is lower in these cells than in others . .
[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 64, 109 ], "type": "Disease" } ]	An arylsulfatase A ( ARSA ) missense mutation ( T274M ) causing late - infantile metachromatic leukodystrophy .
[ { "name": "Metachromatic leukodystrophy", "pos": [ 0, 28 ], "type": "Disease" }, { "name": "MLD", "pos": [ 31, 34 ], "type": "Disease" }, { "name": "autosomal recessive lysosomal storage disorder", "pos": [ 43, 89 ], "type": "Disease" }, { "name": "deficiency of arylsulfatase A", "pos": [ 102, 131 ], "type": "Disease" } ]	Metachromatic leukodystrophy ( MLD ) is an autosomal recessive lysosomal storage disorder caused by a deficiency of arylsulfatase A ( ARSA ; EC 3 . 1 . 6 . 8 ) .
[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 68, 113 ], "type": "Disease" } ]	The 8 ARSA exons and adjacent intron boundaries from a patient with late - infantile metachromatic leukodystrophy were polymerase chain reaction ( PCR ) amplified in seven discrete reactions .
[]	Amplified ARSA exons were analysed for the presence of sequence alterations by single - strand conformation polymorphism analysis , followed by direct sequencing of PCR products .
[]	The patient was found to be homozygous for a C - - > T transition in exon IV that results in the substitution of a highly conserved threonine residue at amino acid 274 with a methionine ( T274M ) .
[ { "name": "MLD", "pos": [ 25, 28 ], "type": "Disease" } ]	Analysis of a further 29 MLD patients revealed the presence of five additional homozygotes for T274M .
[]	All 6 T274M homozygotes ( representing four families ) were of Lebanese descent , and all were known to be the result of consanguineous marriages .
[]	The altered amino acid is rigidly conserved among 10 sulfatases from Escherichia coli to humans ; therefore , it is most likely that the resultant mutant protein will have little or no enzyme activity .
[]	This is consistent with the very low ARSA activity measured in these patients and their uniformly severe clinical presentation
[ { "name": "aniridia", "pos": [ 55, 63 ], "type": "Disease" } ]	Mutations in the PAX6 gene in patients with hereditary aniridia .
[ { "name": "aniridia", "pos": [ 82, 90 ], "type": "Disease" } ]	The 14 exons of the PAX6 gene have been analysed exon - by - exon using SSCP in 6 aniridia families .
[]	In each family band shifts were observed on the SSCP gels for only one exon and direct PCR - sequencing revealed mutations in each case .
[]	Two mutations involved C - - > T transitions in CGAarg codons in exons 9 and 11 .
[]	Another C - - > T transition converted a CAG - glutamine to a TAG - stop in exon 7 .
[]	Small insertions created frameshifts which produced downstream stop codons in another two patients and an A - - > T mutation disrupted the splice donor site of exon 5 in the remaining family .
[]	Thus , complete inactivation of the PAX6 gene is predicted in all cases .

[]

The splice - site mutation would lead to skipping of exon 3 , accompanied by a frameshift , and thus would produce aberrant ASPA .

[ { "name": "Canavan", "pos": [ 21, 28 ], "type": "Disease" } ]

Of the 128 unrelated Canavan chromosomes analyzed , 88 were from probands of Ashkenazi Jewish descent .

[]

The glu285 - - > ala mutation was predominant ( 82 . 9 % ) in this population , followed by the tyr231 - - > ter ( 14 . 8 % ) and 433 - - 2 ( A - - > G ) ( 1 . 1 % ) mutations .

[]

The three mutations account for 98 .

[ { "name": "Canavan", "pos": [ 11, 18 ], "type": "Disease" } ]

8 % of the Canavan chromosomes of Ashkenazi Jewish origin .

[]

The ala305 - - > glu mutation was found exclusively in non - Jewish probands of European descent and constituted 60 % of the 40 mutant chromosomes .

[ { "name": "Canavan disease", "pos": [ 98, 113 ], "type": "Disease" } ]

Predominant occurrence of certain mutations among Ashkenazi Jewish and non - Jewish patients with Canavan disease would suggest a founding - father effect in propagation of these mutant chromosomes

[ { "name": "myotonic dystrophy", "pos": [ 33, 51 ], "type": "Disease" } ]

Intelligence quotient profile in myotonic dystrophy , intergenerational deficit , and correlation with CTG amplification .

[ { "name": "myotonic dystrophy", "pos": [ 155, 173 ], "type": "Disease" }, { "name": "DM", "pos": [ 176, 178 ], "type": "Disease" }, { "name": "DM", "pos": [ 268, 270 ], "type": "Disease" } ]

An abbreviated Wechsler Adult Intelligence Scale Revised ( WAIS - R ) was used to assess verbal and arithmetical cognitive performance in 55 subjects with myotonic dystrophy ( DM ) , covering all grades of disease severity , and 31 controls at 50 % risk of inheriting DM .

[]

Scaled scores from the assessment were converted into an intelligence quotient ( IQ ) estimation on each person .

[ { "name": "DM", "pos": [ 59, 61 ], "type": "Disease" } ]

Significant IQ differences were found between ( 1 ) all 55 DM subjects ( mean 90 . 2 , SD 16 . 1 ) and 31 controls ( 102 . 6 , SD 9 . 4 ) , with no sex differences in either group ; ( 2 ) 15 affected parents ( 99 . 3 , SD 12 . 2 ) and their affected children ( 88 . 1 , SD 17 . 2 ) , where significance was dependent on parental sex being female ; and ( 3 ) 15 pairs of affected sibs ( 89 . 6 , SD 13 . 2 ) and their normal sibs ( 100 . 2 , SD 7 . 6 ) .

[]

IQ steadily declined as ( 1 ) the age of onset of signs and symptoms decreased , and ( 2 ) the CTG expansion size increased .

[]

The correlation appeared to be more linear with age of onset .

[ { "name": "DM", "pos": [ 74, 76 ], "type": "Disease" } ]

The correlation of IQ difference and CTG expansion difference in both the DM parent - child pairs and normal sib - affected sib pairs was poor , indicating that CTG expansion is not a reliable predictor of IQ either in individual persons or families .

[ { "name": "DM", "pos": [ 42, 44 ], "type": "Disease" } ]

Further analysis of cognitive function in DM is required to clarify specific deficits characteristic of this patient group

[ { "name": "Adenomatous polyposis coli", "pos": [ 0, 26 ], "type": "Disease" } ]

Adenomatous polyposis coli and a cytogenetic deletion of chromosome 5 resulting from a maternal intrachromosomal insertion .

[ { "name": "autism", "pos": [ 110, 116 ], "type": "Disease" } ]

We present the clinical and laboratory findings in an institutionalised adult patient originally referred for autism .

[ { "name": "colorectal cancer", "pos": [ 15, 32 ], "type": "Disease" }, { "name": "APC", "pos": [ 198, 201 ], "type": "Disease" } ]

A high risk of colorectal cancer was predicted when an interstitial deletion of the long arm of chromosome 5 , del ( 5 ) ( q15q22 . 3 ) , was detected in her lymphocytes and deletion of the MCC and APC genes confirmed by molecular analysis .

[ { "name": "Adenomatous polyposis coli", "pos": [ 0, 26 ], "type": "Disease" }, { "name": "carcinoma of the rectum", "pos": [ 31, 54 ], "type": "Disease" } ]

Adenomatous polyposis coli and carcinoma of the rectum were subsequently diagnosed in the patient .

[ { "name": "mentally retarded", "pos": [ 19, 36 ], "type": "Disease" }, { "name": "autistic", "pos": [ 39, 47 ], "type": "Disease" }, { "name": "dysmorphic features", "pos": [ 64, 83 ], "type": "Disease" } ]

She was profoundly mentally retarded , autistic , and had minor dysmorphic features consistent with those of previous patients with similar deletions .

[]

The deletion arose as a result of recombination within the small insertion loop formed at meiosis by the direct insertion ( dir ins ( 5 ) ( q22 . 3q14 . 2q15 ) ) found in the patients mother .

[ { "name": "APC", "pos": [ 69, 72 ], "type": "Disease" } ]

This family further confirms the cytogenetic mapping of both MCC and APC genes to 5q22 and comparison with other recent cases suggests that both genes and their closely linked markers lie within the 5q22 .

[]

1 subband

[ { "name": "Familial male breast cancer", "pos": [ 0, 27 ], "type": "Disease" } ]

Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q .

[ { "name": "Breast cancer", "pos": [ 0, 13 ], "type": "Disease" } ]

Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis .

[ { "name": "male breast cancer", "pos": [ 55, 73 ], "type": "Disease" }, { "name": "hereditary breast and ovarian cancer", "pos": [ 93, 129 ], "type": "Disease" } ]

We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus , BRCA1 , on chromosome 17q .

[]

We found strong evidence against linkage to BRCA1 ( lod score - 16 . 63 ) and the best estimate of the proportion of linked families was 0 % ( 95 % CI 0 - 18 % ) .

[ { "name": "breast cancer", "pos": [ 100, 113 ], "type": "Disease" }, { "name": "male breast cancer", "pos": [ 158, 176 ], "type": "Disease" } ]

Our results indicate that there is a gene ( s ) other than BRCA1 which predisposes to early - onset breast cancer in women and which confers a higher risk of male breast cancer .

[ { "name": "male breast cancer", "pos": [ 61, 79 ], "type": "Disease" } ]

Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene .

[ { "name": "Ewing family of tumors", "pos": [ 27, 49 ], "type": "Disease" }, { "name": "malignant melanoma of soft parts", "pos": [ 52, 84 ], "type": "Disease" }, { "name": "desmoplastic small round cell tumors", "pos": [ 89, 125 ], "type": "Disease" } ]

The EWS gene , involved in Ewing family of tumors , malignant melanoma of soft parts and desmoplastic small round cell tumors , codes for an RNA binding protein with novel regulatory domains .

[ { "name": "solid tumors", "pos": [ 102, 114 ], "type": "Disease" }, { "name": "Ewing sarcoma", "pos": [ 125, 138 ], "type": "Disease" }, { "name": "neuroectodermal tumors", "pos": [ 159, 181 ], "type": "Disease" }, { "name": "malignant melanoma of soft parts", "pos": [ 184, 216 ], "type": "Disease" }, { "name": "desmoplastic small round cell tumors", "pos": [ 221, 257 ], "type": "Disease" } ]

The EWS gene , which maps to band q12 of human chromosome 22 , is involved in a wide variety of human solid tumors including Ewing sarcoma , related primitive neuroectodermal tumors , malignant melanoma of soft parts and desmoplastic small round cell tumors .

[ { "name": "tumors", "pos": [ 9, 15 ], "type": "Disease" } ]

In these tumors , the EWS is fused to genes encoding transcriptional activators / repressors , like Fli - 1 or erg or ATF 1 or wt1 .

[]

To better understand the function of the EWS protein , we cloned the EWS cDNA .

[]

Sequence analysis of this cDNA revealed differential splicing involving two exons encoding 72 amino acids .

[]

Both alternatively spliced transcripts , EWS and EWS - b , are expressed in a variety of cells .

[]

Because EWS proteins contain putative conserved RNA binding motifs , we studied the RNA binding properties of the EWS protein .

[]

The EWS - b protein binds to RNA in vitro and , specifically , to poly G and poly U .

[]

The RNA binding activity was localized to the carboxy terminal 86 amino acids , which constitute RGG box .

[]

Thus the amino terminal domain of EWS ( NTD - EWS ) , which is involved in chromosome translocation may regulate the specificity of RNA binding activity of EWS .

[ { "name": "Ewings sarcoma", "pos": [ 50, 64 ], "type": "Disease" } ]

An EWS - erg chimeric protein , which is found in Ewings sarcoma cells , functions as a transcriptional activator .

[]

Mutational analysis of EWS - erg chimeric protein revealed that NTD - EWS functions as a regulatory domain for the transcriptional activation properties of EWS - erg chimeric protein . .

[ { "name": "Canavan disease", "pos": [ 0, 15 ], "type": "Disease" } ]

Canavan disease : genomic organization and localization of human ASPA to 17p13 - ter and conservation of the ASPA gene during evolution .

[ { "name": "Canavan disease", "pos": [ 0, 15 ], "type": "Disease" }, { "name": "spongy degeneration of the brain", "pos": [ 21, 53 ], "type": "Disease" }, { "name": "leukodystrophy", "pos": [ 68, 82 ], "type": "Disease" }, { "name": "deficiency of aspartoacylase", "pos": [ 97, 125 ], "type": "Disease" } ]

Canavan disease , or spongy degeneration of the brain , is a severe leukodystrophy caused by the deficiency of aspartoacylase ( ASPA ) .

[ { "name": "Canavan disease", "pos": [ 95, 110 ], "type": "Disease" } ]

Recently , a missense mutation was identified in human ASPA coding sequence from patients with Canavan disease .

[]

The human ASPA gene has been cloned and found to span 29 kb of the genome .

[]

Human aspartoacylase is coded by six exons intervened by five introns .

[]

The exons vary from 94 ( exon III ) to 514 ( exon VI ) bases .

[]

The exon / intron splice junction sites follow the gt / ag consensus sequence rule .

[]

Southern blot analysis of genomic DNA from human / mouse somatic cell hybrid cell lines localized ASPA to human chromosome 17 .

[]

The human ASPA locus was further mapped in the 17p13 - ter region by fluorescence in situ hybridization .

[]

The bovine aspa gene has also been cloned , and its exon / intron organization is identical to that of the human gene .

[]

The 500 - base sequence upstream of the initiator ATG codon in the human gene and that in the bovine gene are 77 % identical .

[]

Human ASPA coding sequences cross - hybridize with genomic DNA from yeast , chicken , rabbit , cow , dog , mouse , rat , and monkey .

[]

The specificity of cross - species hybridization of coding sequences suggests that aspartoacylase has been conserved during evolution .

[ { "name": "Canavan disease", "pos": [ 96, 111 ], "type": "Disease" } ]

It should now be possible to identify mutations in the noncoding genomic sequences that lead to Canavan disease and to study the regulation of ASPA . .

[ { "name": "Myotonic dystrophy", "pos": [ 0, 18 ], "type": "Disease" } ]

Myotonic dystrophy : size - and sex - dependent dynamics of CTG meiotic instability , and somatic mosaicism .

[ { "name": "Myotonic dystrophy", "pos": [ 0, 18 ], "type": "Disease" }, { "name": "DM", "pos": [ 21, 23 ], "type": "Disease" }, { "name": "neuromuscular disorder", "pos": [ 43, 65 ], "type": "Disease" }, { "name": "DM", "pos": [ 175, 177 ], "type": "Disease" } ]

Myotonic dystrophy ( DM ) is a progressive neuromuscular disorder which results from elongations of an unstable ( CTG ) n repeat , located in the 3 untranslated region of the DM gene .

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A correlation has been demonstrated between the increase in the repeat number of this sequence and the severity of the disease .

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However , the clinical status of patients cannot be unambiguously ascertained solely on the basis of the number of CTG repeats .

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Moreover , the exclusive maternal inheritance of the congenital form remains unexplained .

[ { "name": "DM", "pos": [ 56, 58 ], "type": "Disease" } ]

Our observation of differently sized repeats in various DM tissues from the same individual may explain why the size of the mutation observed in lymphocytes does not necessarily correlate with the severity and nature of symptoms .

[ { "name": "DM", "pos": [ 68, 70 ], "type": "Disease" } ]

Through a molecular and genetic study of 142 families including 418 DM patients , we have investigated the dynamics of the CTG repeat meiotic instability .

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A positive correlation between the size of the repeat and the intergenerational enlargement was observed similarly through male and female meioses for < or = 0 .

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5 - kb CTG sequences .

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Beyond 0 .

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5 kb , the intergenerational variation was more important through female meioses , whereas a tendency to compression was observed almost exclusively in male meioses , for > or = 1 .

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5 - kb fragments .

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This implies a size - and sex - dependent meiotic instability .

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Moreover , segregation analysis supports the hypothesis of a maternal as well as a familial predisposition for the occurrence of the congenital form .

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Finally , this analysis reveals a significant excess of transmitting grandfathers partially accounted for by increased fertility in affected males

[ { "name": "phenylketonuria", "pos": [ 115, 130 ], "type": "Disease" } ]

Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria .

[ { "name": "hyperphenylalaninemic", "pos": [ 153, 174 ], "type": "Disease" } ]

Taking advantage of the illegitimate transcription of the phenylalanine hydroxylase ( PAH ) gene , we have been able to analyse the PAH cDNA sequence of hyperphenylalaninemic children in circulating lymphocytes .

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Using this approach , we have also identified 3 novel mutations in cDNA from liver and lymphocytes of two patients .

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One mutation , detected by the abnormal pattern of migration of an amplified fragment , is a C to T transition in the splice acceptor site of intron 10 , which resulted in the skipping of exon 11 with the premature termination of RNA translation downstream from exon 12 ( - 3 IVS10 ) .

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The other two mutations are missense mutations in exons 10 and 11 ( respectively , L333F and E390G ) .

[ { "name": "phenylketonuria", "pos": [ 242, 257 ], "type": "Disease" } ]

The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria . .

[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 66, 111 ], "type": "Disease" } ]

High residual arylsulfatase A ( ARSA ) activity in a patient with late - infantile metachromatic leukodystrophy .

[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 39, 84 ], "type": "Disease" }, { "name": "MLD", "pos": [ 87, 90 ], "type": "Disease" } ]

We identified a patient suffering from late - infantile metachromatic leukodystrophy ( MLD ) who has a residual arylsulfatase A ( ARSA ) activity of about 10 % .

[ { "name": "adult MLD", "pos": [ 93, 102 ], "type": "Disease" } ]

Fibroblasts of the patient show significant sulfatide degradation activity exceeding that of adult MLD patients .

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Analysis of the ARSA gene in this patient revealed heterozygosity for two new mutant alleles in one allele , deletion of C 447 in exon 2 leads to a frameshift and to a premature stop codon at amino acid position 105 ; in the second allele , a G - - > A transition in exon 5 causes a Gly309 - - > Ser substitution .

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Transient expression of the mutant Ser309 - ARSA resulted in only 13 % enzyme activity of that observed in cells expressing normal ARSA .

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The mutant ARSA is correctly targeted to the lysosomes but is unstable .

[ { "name": "late - infantile type of MLD", "pos": [ 68, 96 ], "type": "Disease" } ]

These findings are in contrast to previous results showing that the late - infantile type of MLD is always associated with the complete absence of ARSA activity .

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The expression of the mutant ARSA protein may be influenced by particular features of oligodendrocytes , such that the level of mutant enzyme is lower in these cells than in others . .

[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 64, 109 ], "type": "Disease" } ]

An arylsulfatase A ( ARSA ) missense mutation ( T274M ) causing late - infantile metachromatic leukodystrophy .

[ { "name": "Metachromatic leukodystrophy", "pos": [ 0, 28 ], "type": "Disease" }, { "name": "MLD", "pos": [ 31, 34 ], "type": "Disease" }, { "name": "autosomal recessive lysosomal storage disorder", "pos": [ 43, 89 ], "type": "Disease" }, { "name": "deficiency of arylsulfatase A", "pos": [ 102, 131 ], "type": "Disease" } ]

Metachromatic leukodystrophy ( MLD ) is an autosomal recessive lysosomal storage disorder caused by a deficiency of arylsulfatase A ( ARSA ; EC 3 . 1 . 6 . 8 ) .

[ { "name": "late - infantile metachromatic leukodystrophy", "pos": [ 68, 113 ], "type": "Disease" } ]

The 8 ARSA exons and adjacent intron boundaries from a patient with late - infantile metachromatic leukodystrophy were polymerase chain reaction ( PCR ) amplified in seven discrete reactions .

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Amplified ARSA exons were analysed for the presence of sequence alterations by single - strand conformation polymorphism analysis , followed by direct sequencing of PCR products .

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The patient was found to be homozygous for a C - - > T transition in exon IV that results in the substitution of a highly conserved threonine residue at amino acid 274 with a methionine ( T274M ) .

[ { "name": "MLD", "pos": [ 25, 28 ], "type": "Disease" } ]

Analysis of a further 29 MLD patients revealed the presence of five additional homozygotes for T274M .

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All 6 T274M homozygotes ( representing four families ) were of Lebanese descent , and all were known to be the result of consanguineous marriages .

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The altered amino acid is rigidly conserved among 10 sulfatases from Escherichia coli to humans ; therefore , it is most likely that the resultant mutant protein will have little or no enzyme activity .

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This is consistent with the very low ARSA activity measured in these patients and their uniformly severe clinical presentation

[ { "name": "aniridia", "pos": [ 55, 63 ], "type": "Disease" } ]

Mutations in the PAX6 gene in patients with hereditary aniridia .

[ { "name": "aniridia", "pos": [ 82, 90 ], "type": "Disease" } ]

The 14 exons of the PAX6 gene have been analysed exon - by - exon using SSCP in 6 aniridia families .

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In each family band shifts were observed on the SSCP gels for only one exon and direct PCR - sequencing revealed mutations in each case .

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Two mutations involved C - - > T transitions in CGAarg codons in exons 9 and 11 .

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Another C - - > T transition converted a CAG - glutamine to a TAG - stop in exon 7 .

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Small insertions created frameshifts which produced downstream stop codons in another two patients and an A - - > T mutation disrupted the splice donor site of exon 5 in the remaining family .

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Thus , complete inactivation of the PAX6 gene is predicted in all cases .