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[] | Conventional PCR and direct sequencing then established the intron - exon borders of the mutant genomic DNA revealing two splice acceptor mutations a G - - > C substitution at position - 1 of intron 4 and an A - - > G substitution at position - 2 of intron 6 . |
[
{
"name": "prolidase deficiency",
"pos": [
45,
65
],
"type": "Disease"
}
] | Our results indicate that the severe form of prolidase deficiency is caused by multiple PEPD alleles . |
[] | In this report we attempt to begin the process of describing these alleles and cataloging their phenotypic expression . . |
[
{
"name": "Friedreich ataxia",
"pos": [
65,
82
],
"type": "Disease"
}
] | Recombinations in individuals homozygous by descent localize the Friedreich ataxia locus in a cloned 450 - kb interval . |
[
{
"name": "Friedreich ataxia",
"pos": [
14,
31
],
"type": "Disease"
},
{
"name": "FRDA",
"pos": [
34,
38
],
"type": "Disease"
},
{
"name": "neurodegenerative disease",
"pos": [
52,
77
],
"type": "Disease"
}
] | The locus for Friedreich ataxia ( FRDA ) , a severe neurodegenerative disease , is tightly linked to markers D9S5 and D9S15 , and analysis of rare recombination events has suggested the order cen - FRDA - D9S5 - D9S15 - qter . |
[] | We report here the construction of a YAC contig extending 800 kb centromeric to D9S5 and the isolation of five new microsatellite markers from this region . |
[
{
"name": "FRDA",
"pos": [
50,
54
],
"type": "Disease"
},
{
"name": "FRDA",
"pos": [
164,
168
],
"type": "Disease"
}
] | In order to map these markers with respect to the FRDA locus , all within a 1 - cM confidence interval , we sought to increase the genetic information of available FRDA families by considering homozygosity by descent and association with founder haplotypes in isolated populations . |
[
{
"name": "FRDA",
"pos": [
212,
216
],
"type": "Disease"
}
] | This approach allowed us to identify one phase - known recombination and one probable historic recombination on haplotypes from Reunion Island patients , both of which place three of the five markers proximal to FRDA . |
[
{
"name": "FRDA",
"pos": [
50,
54
],
"type": "Disease"
}
] | This represents the first identification of close FRDA flanking markers on the centromeric side . |
[] | The two other markers allowed us to narrow the breakpoint of a previously identified distal recombination that is > 180 kb from D9S5 ( 26P ) . |
[
{
"name": "FRDA",
"pos": [
39,
43
],
"type": "Disease"
}
] | Taken together , the results place the FRDA locus in a 450 - kb interval , which is small enough for direct search of candidate genes . |
[] | A detailed rare cutter restriction map and a cosmid contig covering this interval were constructed and should facilitate the search of genes in this region . . |
[
{
"name": "Prader - Willi syndrome",
"pos": [
67,
90
],
"type": "Disease"
}
] | Investigation of thermoregulatory characteristics in patients with Prader - Willi syndrome . |
[
{
"name": "Prader - Willi syndrome",
"pos": [
94,
117
],
"type": "Disease"
},
{
"name": "PWS",
"pos": [
120,
123
],
"type": "Disease"
},
{
"name": "PWS",
"pos": [
163,
166
],
"type": "Disease"
},
{
"name": "neurodevelopmentally handicapped",
"pos": [
186,
218
],
"type": "Disease"
}
] | A survey instrument is used to assess temperature regulation characteristics in children with Prader - Willi syndrome ( PWS ) compared to 3 control groups sibs of PWS patients ( SIB ) , neurodevelopmentally handicapped children ( ND ) , and age and gender matched well children ( WC ) . |
[
{
"name": "PWS",
"pos": [
43,
46
],
"type": "Disease"
}
] | Significant differences were found between PWS patients , SIB controls , and WC controls in the prevalence of febrile convulsions , fever - associated symptoms , and temperature less than 94 degrees F . |
[
{
"name": "PWS",
"pos": [
54,
57
],
"type": "Disease"
},
{
"name": "PWS",
"pos": [
143,
146
],
"type": "Disease"
},
{
"name": "neurodevelopmentally handicapped",
"pos": [
170,
202
],
"type": "Disease"
},
{
"name": "hypothalamic abnormalities",
"pos": [
288,
314
],
"type": "Disease"
}
] | No differences were noted in any variable between the PWS patients and the ND controls , suggesting that these abnormalities are not unique to PWS , but can occur in any neurodevelopmentally handicapped individual , further suggesting these do not necessarily reflect syndrome - specific hypothalamic abnormalities . . |
[
{
"name": "retinitis pigmentosa",
"pos": [
31,
51
],
"type": "Disease"
},
{
"name": "pattern dystrophy",
"pos": [
54,
71
],
"type": "Disease"
},
{
"name": "fundus flavimaculatus",
"pos": [
78,
99
],
"type": "Disease"
}
] | Phenotypic variation including retinitis pigmentosa , pattern dystrophy , and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin / RDS gene . |
[
{
"name": "autosomal dominant retinitis pigmentosa",
"pos": [
87,
126
],
"type": "Disease"
},
{
"name": "macular dystrophy",
"pos": [
137,
154
],
"type": "Disease"
},
{
"name": "retinitis punctata albescens",
"pos": [
161,
189
],
"type": "Disease"
}
] | BACKGROUND AND OBJECTIVES Mutations of the peripherin / RDS gene have been reported in autosomal dominant retinitis pigmentosa , pattern macular dystrophy , and retinitis punctata albescens . |
[] | We report herein the occurrence of three separate phenotypes within a single family with a novel 3 - base pair deletion of codon 153 or 154 of the peripherin / RDS gene . |
[] | DESIGN Case reports with clinical features , fluorescein angiography , kinetic perimetry , electrophysiological studies , and molecular genetics . |
[] | SETTING University medical centers . |
[] | PATIENTS A 75 - year - old woman , her two daughters ( aged 44 and 50 years ) , and her 49 - year - old son were screened for peripherin / RDS mutations because of the presence of multiple phenotypes within the same family . |
[
{
"name": "retinitis pigmentosa",
"pos": [
116,
136
],
"type": "Disease"
}
] | RESULTS The mother presented at age 63 years with a profoundly abnormal electroretinogram ( ERG ) and adult - onset retinitis pigmentosa that progressed dramatically over 12 years , with marked loss of peripheral visual field . |
[
{
"name": "pattern macular dystrophy",
"pos": [
23,
48
],
"type": "Disease"
}
] | One daughter developed pattern macular dystrophy at age 31 years . |
[] | At age 44 years , her ERG was moderately abnormal but her clinical disease was limited to the macula . |
[
{
"name": "macular degeneration",
"pos": [
48,
68
],
"type": "Disease"
},
{
"name": "fundus flavimaculatus",
"pos": [
121,
142
],
"type": "Disease"
}
] | Another daughter presented at age 42 years with macular degeneration and over 10 years developed the clinical picture of fundus flavimaculatus . |
[] | Her peripheral visual field was preserved but her ERG was moderately abnormal . |
[
{
"name": "macular degeneration",
"pos": [
21,
41
],
"type": "Disease"
}
] | The son had onset of macular degeneration at age 44 years . |
[
{
"name": "Pericentral scotomas",
"pos": [
0,
20
],
"type": "Disease"
}
] | Pericentral scotomas were present and the ERG was markedly abnormal . |
[] | Fluorescein angiography revealed punctate pigment epithelial transmission defects . |
[] | CONCLUSIONS A 3 - base pair deletion of codon 153 or 154 of the peripherin / RDS gene can produce clinically disparate phenotypes even within the same family . . |
[] | Assignment of the human Na + / glucose cotransporter gene SGLT1 to chromosome 22q13 . 1 . |
[] | The Na + / glucose cotransporter gene SGLT1 encodes the primary carrier protein responsible for the uptake of the dietary sugars glucose and galactose from the intestinal lumen . |
[] | SGLT1 transport activity is currently exploited in oral rehydration therapy . |
[] | The 75 - kDa glycoprotein is localized in the brush border of the intestinal epithelium and is predicted to comprise 12 membrane spans . |
[
{
"name": "autosomal recessive disease glucose / galactose malabsorption",
"pos": [
25,
86
],
"type": "Disease"
}
] | In two patients with the autosomal recessive disease glucose / galactose malabsorption , the underlying cause was found to be a missense mutation in SGLT1 , and the Asp28 - - > Asn change was demonstrated in vitro to eliminate SGLT1 transport activity . |
[] | The SGLT1 gene was previously shown to reside on the distal q arm of chromosome 22 ( 11 . 2 - - > qter ) . |
[] | We have used a cosmid probe for fluorescence in situ hybridization , which refines the localization to 22q13 . |
[
{
"name": "genetic diseases",
"pos": [
81,
97
],
"type": "Disease"
}
] | 1 , and provide an example of the utility of the SGLT1 probe as a diagnostic for genetic diseases associated with translocations of chromosome 22 . |
[
{
"name": "APC",
"pos": [
63,
66
],
"type": "Disease"
},
{
"name": "adenomatous polyposis coli",
"pos": [
80,
106
],
"type": "Disease"
}
] | Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients . |
[
{
"name": "tumor",
"pos": [
30,
35
],
"type": "Disease"
},
{
"name": "APC",
"pos": [
54,
57
],
"type": "Disease"
},
{
"name": "adenomatous polyposis coli",
"pos": [
67,
93
],
"type": "Disease"
},
{
"name": "colorectal cancer",
"pos": [
134,
151
],
"type": "Disease"
}
] | In humans , alteration of the tumor suppressor gene , APC , causes adenomatous polyposis coli , a condition causing predisposition to colorectal cancer . |
[
{
"name": "congenital hypertrophy of the retinal pigment epithelium",
"pos": [
65,
121
],
"type": "Disease"
},
{
"name": "CHRPE",
"pos": [
124,
129
],
"type": "Disease"
}
] | The syndrome inconsistently associates characteristic patches of congenital hypertrophy of the retinal pigment epithelium ( CHRPE ) . |
[
{
"name": "CHRPE",
"pos": [
53,
58
],
"type": "Disease"
}
] | Ocular examination revealed that patients expressing CHRPE tend to cluster within specific families . |
[
{
"name": "APC",
"pos": [
10,
13
],
"type": "Disease"
}
] | The exact APC mutation was identified in 42 unrelated patients . |
[] | In all cases these mutations were predicted to lead to the synthesis of a truncated protein . |
[
{
"name": "CHRPE",
"pos": [
14,
19
],
"type": "Disease"
}
] | The extent of CHRPE was found to be dependent on the position of the mutation along the coding sequence . |
[
{
"name": "CHRPE",
"pos": [
0,
5
],
"type": "Disease"
}
] | CHRPE lesions are almost always absent if the mutation occurs before exon 9 , but are systematically present if it occurs after this exon . |
[
{
"name": "APC",
"pos": [
135,
138
],
"type": "Disease"
}
] | Thus , the range of phenotypic expression observed among affected patients may result in part from different allelic manifestations of APC mutations . . |
[] | The effects of dystrophin gene mutations on the ERG in mice and humans . |
[] | PURPOSE . |
[
{
"name": "Duchenne muscular dystrophy",
"pos": [
83,
110
],
"type": "Disease"
},
{
"name": "DMD",
"pos": [
113,
116
],
"type": "Disease"
},
{
"name": "DMD",
"pos": [
196,
199
],
"type": "Disease"
}
] | The authors earlier findings of a negative electroretinogram ( ERG ) in a boy with Duchenne muscular dystrophy ( DMD ) led them to investigate dystrophin gene deletions and ERGs in five boys with DMD . |
[
{
"name": "DMD",
"pos": [
96,
99
],
"type": "Disease"
}
] | The authors wanted to determined whether there were similar ERG findings in an animal model for DMD , the mdx mouse . |
[] | METHODS . |
[
{
"name": "DMD",
"pos": [
46,
49
],
"type": "Disease"
}
] | Ganzfeld ERGs were recorded in five boys with DMD after a complete ophthalmic examination . |
[] | The dystrophin gene was analyzed by Southern blot hybridization . |
[] | ERGs were recorded in anesthetized mdx and control mice with a modified Grass photostimulator ( Grass Instrument Company , Quincy , MA ) . |
[] | RESULTS . |
[] | Ophthalmic examinations in all five boys had normal findings , yet an abnormal negative ERG was recorded for each subject . |
[] | The subjects gene deletions were variable , ranging from large deletions to no detectable deletions . |
[] | The ERGs of the mdx mice were normal and did not differ significantly from those of the control mice . |
[] | CONCLUSIONS . |
[
{
"name": "DMD",
"pos": [
89,
92
],
"type": "Disease"
}
] | The authors believe the unique ERG recorded for the human subjects is a manifestation of DMD associated with defects at the dystrophin gene locus and represents a new clinical entity . |
[] | The ERG of the mdx mouse may be spared for several reasons , including milder effects of the mouse gene defect , differences in muscle and retinal gene product , or species differences in the biochemical role of dystrophin . |
[
{
"name": "DMD",
"pos": [
68,
71
],
"type": "Disease"
}
] | The ERG shows promise of becoming a noninvasive diagnostic tool for DMD and its milder allelic forms . . |
[
{
"name": "APC tumor",
"pos": [
19,
28
],
"type": "Disease"
}
] | Association of the APC tumor suppressor protein with catenins . |
[
{
"name": "colorectal cancer",
"pos": [
74,
91
],
"type": "Disease"
}
] | Mutations of APC appear to initiate sporadic and inherited forms of human colorectal cancer . |
[
{
"name": "APC",
"pos": [
98,
101
],
"type": "Disease"
}
] | Although these mutations have been well characterized , little is known about the function of the APC gene product . |
[
{
"name": "APC",
"pos": [
42,
45
],
"type": "Disease"
}
] | Two cellular proteins that associate with APC were identified by nucleotide sequence analysis and peptide mapping as the E - cadherin - associated proteins alpha - and beta - catenin . |
[] | A 27 - residue fragment of APC containing a 15 - amino acid repeat was sufficient for the interaction with the catenins . |
[
{
"name": "tumor",
"pos": [
48,
53
],
"type": "Disease"
}
] | These results suggest an important link between tumor initiation and cell adhesion . . |
[
{
"name": "Angelman syndrome",
"pos": [
106,
123
],
"type": "Disease"
},
{
"name": "Prader - Willi syndrome",
"pos": [
128,
151
],
"type": "Disease"
}
] | Difference in methylation patterns within the D15S9 region of chromosome 15q11 - 13 in first cousins with Angelman syndrome and Prader - Willi syndrome . |
[
{
"name": "Angelman syndrome",
"pos": [
66,
83
],
"type": "Disease"
},
{
"name": "AS",
"pos": [
86,
88
],
"type": "Disease"
},
{
"name": "Prader - Willi syndrome",
"pos": [
95,
118
],
"type": "Disease"
},
{
"name": "PWS",
"pos": [
121,
124
],
"type": "Disease"
}
] | Abnormalities of chromosome region 15q11 - 13 are associated with Angelman syndrome ( AS ) and Prader - Willi syndrome ( PWS ) . |
[
{
"name": "AS",
"pos": [
181,
183
],
"type": "Disease"
},
{
"name": "PWS",
"pos": [
188,
191
],
"type": "Disease"
}
] | Differences between the methylation patterns of the region of chromosome 15q11 - 13 which hybridizes to the highly conserved DNA , DN34 , in normal individuals and in patients with AS and PWS have been described . |
[
{
"name": "AS",
"pos": [
61,
63
],
"type": "Disease"
},
{
"name": "PWS",
"pos": [
68,
71
],
"type": "Disease"
}
] | We report on a family in which first cousins are affected by AS and PWS as a result of a familial paracentric inversion of 15q11 - q13 . |
[] | The results of the studies on this family demonstrate the differences in the methylation patterns in the 2 conditions and the phenomenon of genomic imprinting , whereby genetic information is expressed differently dependent on the parent of origin . . |
[
{
"name": "Wilson disease",
"pos": [
21,
35
],
"type": "Disease"
}
] | Haplotype studies in Wilson disease . |
[
{
"name": "Wilson disease",
"pos": [
20,
34
],
"type": "Disease"
}
] | In 51 families with Wilson disease , we have studied DNA haplotypes of dinucleotide repeat polymorphisms ( CA repeats ) in the 13q14 . |
[
{
"name": "Wilson disease",
"pos": [
61,
75
],
"type": "Disease"
},
{
"name": "WND",
"pos": [
83,
86
],
"type": "Disease"
}
] | 3 region , to examine these markers for association with the Wilson disease gene ( WND ) . |
[
{
"name": "WND",
"pos": [
162,
165
],
"type": "Disease"
}
] | In addition to a marker ( D13S133 ) described elsewhere , we have developed three new highly polymorphic markers ( D13S314 , D13S315 , and D13S316 ) close to the WND locus . |
[
{
"name": "WND",
"pos": [
185,
188
],
"type": "Disease"
}
] | We have examined the distribution of marker alleles at the loci studied and have found that D13S314 , D13S133 , and D13S316 each show nonrandom distribution on chromosomes carrying the WND mutation . |
[
{
"name": "WND",
"pos": [
119,
122
],
"type": "Disease"
}
] | We have studied haplotypes of these three markers and have found that there are highly significant differences between WND and normal haplotypes in northern European families . |
[
{
"name": "Wilson disease",
"pos": [
107,
121
],
"type": "Disease"
}
] | These findings have important implications for mutation detection and molecular diagnosis in families with Wilson disease . |
[] | Genetic analysis of the BRCA1 region in a large breast / ovarian family : refinement of the minimal region containing BRCA1 . |
[
{
"name": "breast / ovarian cancer",
"pos": [
43,
66
],
"type": "Disease"
}
] | We have analyzed a single multi - affected breast / ovarian cancer pedigree ( BOV3 ) and have shown consistent inheritance of markers on chromosome 17q with the disease confirming that this family is due to the BRCA1 gene . |
[
{
"name": "breast cancer",
"pos": [
70,
83
],
"type": "Disease"
}
] | Analysis of 17q haplotypes shows a recombination event in a bilateral breast cancer case which suggests that the BRCA1 gene lies distal to D17S857 ; D17S857 is thus the new proximal boundary for the region containing BRCA1 . |
[] | Combining this information with previously published mapping information suggests that BRCA1 is contained in a region estimated at 1 - 1 . |
[] | 5 Mb in length . |
[
{
"name": "breast tumour",
"pos": [
10,
23
],
"type": "Disease"
},
{
"name": "tumours",
"pos": [
99,
106
],
"type": "Disease"
}
] | All seven breast tumour / blood pairs examined from this family show loss of heterozygosity in the tumours . |
[
{
"name": "tumour",
"pos": [
27,
33
],
"type": "Disease"
},
{
"name": "tumour",
"pos": [
99,
105
],
"type": "Disease"
}
] | The allel retained in each tumour was from the disease - bearing chromosome implicating BRCA1 as a tumour suppressor gene . |
[] | We have sequenced the 17 beta - oestradiol dehydrogenase genes ( EDH17B1 and EDH17B2 ) which have been suggested as candidate genes for BRCA1 in four members of this family . |
[] | No germline mutations were detected . |
[
{
"name": "Myotonic dystrophy",
"pos": [
0,
18
],
"type": "Disease"
}
] | Myotonic dystrophy kinase is a component of neuromuscular junctions . |
[
{
"name": "myotonic dystrophy",
"pos": [
30,
48
],
"type": "Disease"
},
{
"name": "DM",
"pos": [
51,
53
],
"type": "Disease"
}
] | The clinical manifestation of myotonic dystrophy ( DM ) is correlated to the extent of expansion of an unstable [ CTG ] n DNA motif . |
[
{
"name": "myotonic dystrophy",
"pos": [
211,
229
],
"type": "Disease"
}
] | Recent studies have demonstrated that this trinucleotide motif forms part of the last , 3 untranslated exon of a gene which potentially encodes multiple protein isoforms of a serine / threonine protein kinase ( myotonic dystrophy protein kinase , DM - PK ) . |
[] | We report here on the development of antisera against synthetic DM - PK peptide antigens and their use in biochemical and histochemical studies . |
[
{
"name": "DM",
"pos": [
15,
17
],
"type": "Disease"
}
] | Immunoreactive DM - kinase protein of 53 kD is present at low levels in skeletal and cardiac muscle extracts of DM patients and normal controls . |
[] | Immunohistochemical staining revealed that DM - PK is localised prominently at sites of neuromuscular and myotendinous junctions ( NMJs and MTJs ) of human and rodent skeletal muscles . |
[] | Furthermore , very low levels of immunoreactive DM - PK protein are present in the sarcoplasm of predominantly type I fibres in various muscles . |
[
{
"name": "DM",
"pos": [
124,
126
],
"type": "Disease"
}
] | Strikingly , presence of the protein can also be demonstrated for NMJs of muscular tissues of adult and congenital cases of DM , with no gross changes in structural organisation . |
[
{
"name": "DM",
"pos": [
223,
225
],
"type": "Disease"
}
] | Our findings provide a basis for further characterisation of the role of the kinase in protein assembly processes or signal mediation at synaptic sites and ultimately for the understanding of the complex pathophysiology of DM . . |