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[
{
"name": "cholesterol acyltransferase deficiency",
"pos": [
144,
182
],
"type": "Disease"
},
{
"name": "fish - eye disease",
"pos": [
187,
205
],
"type": "Disease"
}
] | Markedly accelerated catabolism of apolipoprotein A - II ( ApoA - II ) and high density lipoproteins containing ApoA - II in classic lecithin : cholesterol acyltransferase deficiency and fish - eye disease . |
[
{
"name": "Classic ( complete ) lecithin cholesterol acyltransferase ( LCAT ) deficiency",
"pos": [
0,
77
],
"type": "Disease"
},
{
"name": "Fish - eye disease",
"pos": [
82,
100
],
"type": "Disease"
},
{
"name": "partial LCAT deficiency",
"pos": [
103,
126
],
"type": "Disease"
},
{
"name": "atherosclerotic cardiovascular disease",
"pos": [
282,
320
],
"type": "Disease"
}
] | Classic ( complete ) lecithin cholesterol acyltransferase ( LCAT ) deficiency and Fish - eye disease ( partial LCAT deficiency ) are genetic syndromes associated with markedly decreased plasma levels of high density lipoprotein ( HDL ) cholesterol but not with an increased risk of atherosclerotic cardiovascular disease . |
[
{
"name": "LCAT deficiency",
"pos": [
122,
137
],
"type": "Disease"
},
{
"name": "classic LCAT deficiency",
"pos": [
149,
172
],
"type": "Disease"
},
{
"name": "Fish - eye disease",
"pos": [
187,
205
],
"type": "Disease"
}
] | We investigated the metabolism of the HDL apolipoproteins ( apo ) apoA - I and apoA - II in a total of five patients with LCAT deficiency , one with classic LCAT deficiency and four with Fish - eye disease . |
[] | Plasma levels of apoA - II were decreased to a proportionately greater extent ( 23 % of normal ) than apoA - I ( 30 % of normal ) . |
[] | In addition , plasma concentrations of HDL particles containing both apoA - I and apoA - II ( LpA - I A - II ) were much lower ( 18 % of normal ) than those of particles containing only apoA - I ( LpA - I ) ( 51 % of normal ) . |
[] | The metabolic basis for the low levels of apoA - II and LpA - I A - II was investigated in all five patients using both exogenous radiotracer and endogenous stable isotope labeling techniques . |
[] | The mean plasma residence time of apoA - I was decreased at 2 . |
[] | 08 + / - 0 . |
[] | 27 d ( controls 4 . 74 + / - 0 . 65 days ) ; however , the residence time of apoA - II was even shorter at 1 . |
[] | 66 + / - 0 . |
[] | 24 d ( controls 5 . 25 + / - 0 . 61 d ) . |
[] | In addition , the catabolism of apoA - I in LpA - I A - II was substantially faster than that of apoA - I in LpA - I . |
[
{
"name": "complete or partial LCAT deficiency",
"pos": [
41,
76
],
"type": "Disease"
}
] | In summary , genetic syndromes of either complete or partial LCAT deficiency result in low levels of HDL through preferential hypercatabolism of apoA - II and HDL particles containing apoA - II . |
[
{
"name": "atherosclerosis",
"pos": [
84,
99
],
"type": "Disease"
},
{
"name": "classic LCAT deficiency",
"pos": [
214,
237
],
"type": "Disease"
},
{
"name": "Fish - eye disease",
"pos": [
242,
260
],
"type": "Disease"
},
{
"name": "atherosclerosis",
"pos": [
301,
316
],
"type": "Disease"
}
] | Because LpA - I has been proposed to be more protective than LpA - I A - II against atherosclerosis , this selective effect on the metabolism of LpA - I A - II may provide a potential explanation why patients with classic LCAT deficiency and Fish - eye disease are not at increased risk for premature atherosclerosis despite markedly decreased levels of HDL cholesterol and apoA - I |
[
{
"name": "X linked recessive thrombocytopenia",
"pos": [
0,
35
],
"type": "Disease"
}
] | X linked recessive thrombocytopenia . |
[
{
"name": "thrombocytopenia",
"pos": [
51,
67
],
"type": "Disease"
}
] | A Saudi Arab boy presented in early childhood with thrombocytopenia , morphologically large and normal sized platelets , increased mean platelet volume , and a hypermegakaryocytic bone marrow . |
[
{
"name": "immunological abnormalities",
"pos": [
65,
92
],
"type": "Disease"
}
] | There was no clinical and laboratory evidence of any significant immunological abnormalities . |
[
{
"name": "X linked recessive thrombocytopenic disorder",
"pos": [
95,
139
],
"type": "Disease"
}
] | Similar findings in two other brothers suggested strongly that they were all suffering from an X linked recessive thrombocytopenic disorder . |
[
{
"name": "Wiskott - Aldrich syndrome",
"pos": [
195,
221
],
"type": "Disease"
},
{
"name": "WAS",
"pos": [
224,
227
],
"type": "Disease"
}
] | Results of DNA analysis with the probe M27 beta are consistent with X linkage and indicate also that the locus of the relevant gene lies close to or is identical to the locus of the gene for the Wiskott - Aldrich syndrome ( WAS ) . |
[
{
"name": "immune deficiencies",
"pos": [
152,
171
],
"type": "Disease"
},
{
"name": "X linked recessive thrombocytopenia",
"pos": [
196,
231
],
"type": "Disease"
},
{
"name": "WAS",
"pos": [
303,
306
],
"type": "Disease"
}
] | Because of various features which include the presence of large and normal sized platelets ( rather than small platelets ) and freedom from significant immune deficiencies , it is likely that the X linked recessive thrombocytopenia in this family is an isolated entity quite distinct from the classical WAS phenotype . |
[
{
"name": "WAS",
"pos": [
39,
42
],
"type": "Disease"
}
] | However , a modified expression of the WAS gene producing a mild phenotypic variant cannot be excluded entirely . . |
[
{
"name": "Macular dystrophy",
"pos": [
0,
17
],
"type": "Disease"
},
{
"name": "retinal degeneration",
"pos": [
70,
90
],
"type": "Disease"
}
] | Macular dystrophy associated with mutations at codon 172 in the human retinal degeneration slow gene . |
[
{
"name": "retinal degeneration",
"pos": [
39,
59
],
"type": "Disease"
},
{
"name": "autosomal dominant retinitis pigmentosa",
"pos": [
146,
185
],
"type": "Disease"
}
] | BACKGROUND Recently , mutations in the retinal degeneration slow ( rds ) gene which codes for peripherin - rds have been implicated as a cause of autosomal dominant retinitis pigmentosa . |
[] | Because this gene is expressed in both rods and cones , mutations in the rds gene might be expected to cause degeneration affecting either the scotopic or photopic systems . |
[
{
"name": "macular dystrophy",
"pos": [
128,
145
],
"type": "Disease"
}
] | Mutations at codon 172 of the rds gene have been identified in three families with autosomal dominantly inherited , progressive macular dystrophy . |
[] | METHODS Affected individuals underwent ophthalmic examination , scotopic perimetry , dark adaptometry , measurement of color - contrast sensitivity , and electroretinography to characterize the photoreceptor dysfunction . |
[
{
"name": "visual loss",
"pos": [
73,
84
],
"type": "Disease"
},
{
"name": "central scotoma",
"pos": [
148,
163
],
"type": "Disease"
},
{
"name": "atrophy of the retinal pigment epithelium",
"pos": [
186,
227
],
"type": "Disease"
},
{
"name": "choriocapillaris of the macula",
"pos": [
232,
262
],
"type": "Disease"
}
] | RESULTS In all but one affected member , symptoms of progressive central visual loss developed in the third or fourth decade of life accompanied by central scotoma and well - demarcated atrophy of the retinal pigment epithelium and choriocapillaris of the macula . |
[] | In general , cone and rod thresholds were elevated , and color - contrast sensitivity was absent in the central visual field . |
[] | Peripherally , the scotopic sensitivities were normal , as was the recovery from bleach . |
[] | Cone electroretinograms were diminished in amplitude , and delayed in all affected adults except one . |
[] | Rod electroretinograms were normal or near normal in amplitude , and had normal implicit times . |
[] | Affected asymptomatic children had macular changes , abnormal color - contrast sensitivity , and reduced pattern and cone electroretinograms . |
[
{
"name": "macular dystrophy",
"pos": [
87,
104
],
"type": "Disease"
},
{
"name": "cone dysfunction",
"pos": [
132,
148
],
"type": "Disease"
}
] | CONCLUSION These results indicate that mutations in the rds gene can be expressed as a macular dystrophy , with evidence of primary cone dysfunction and preservation of peripheral rod function . . |
[
{
"name": "hemochromatosis",
"pos": [
102,
117
],
"type": "Disease"
}
] | Anonymous marker loci within 400 kb of HLA - A generate haplotypes in linkage disequilibrium with the hemochromatosis gene ( HFE ) |
[
{
"name": "hemochromatosis",
"pos": [
4,
19
],
"type": "Disease"
}
] | The hemochromatosis gene ( HFE ) maps to 6p21 . |
[] | 3 and is less than 1 cM from the HLA class I genes ; however , the precise physical location of the gene has remained elusive and controversial . |
[
{
"name": "hemochromatosis",
"pos": [
59,
74
],
"type": "Disease"
}
] | The unambiguous identification of a crossover event within hemochromatosis families is very difficult ; it is particularly hampered by the variability of the phenotypic expression as well as by the sex - and age - related penetrance of the disease . |
[] | For these practical considerations , traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE . |
[] | We therefore embarked upon a linkage - disequilibrium analysis of HFE and normal chromosomes from the Brittany population . |
[
{
"name": "hemochromatosis",
"pos": [
27,
42
],
"type": "Disease"
},
{
"name": "hemochromatosis",
"pos": [
65,
80
],
"type": "Disease"
}
] | In the present report , 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP - typed with a battery of probes , including two newly derived polymorphic markers from the 6 . |
[] | 7 and HLA - F loci located 150 and 250 kb telomeric to HLA - A , respectively . |
[] | The results suggest a strong peak of existing linkage disequilibrium focused within the i82 - to - 6 . |
[] | 7 interval ( approximately 250 kb ) . |
[] | The zone of linkage disequilibrium is flanked by the i97 locus , positioned 30 kb proximal to i82 , and the HLA - F gene , found 250 kb distal to HLA - A , markers of which display no significant association with HFE . |
[] | These data support the possibility that HFE resides within the 400 - kb expanse of DNA between i97 and HLA - F . |
[] | Alternatively , the very tight association of HLA - A3 and allele 1 of the 6 . |
[] | 7 locus , both of which are comprised by the major ancestral or founder HFE haplotype in Brittany , supports the possibility that the disease gene may reside immediately telomeric to the 6 . |
[] | 7 locus within the linkage - disequilibrium zone . |
[
{
"name": "hemochromatosis",
"pos": [
15,
30
],
"type": "Disease"
}
] | Additionally , hemochromatosis haplotypes possessing HLA - A11 and the low - frequency HLA - F polymorphism ( allele 2 ) are supportive of a separate founder chromosome containing a second , independently arising mutant allele . |
[
{
"name": "hemochromatosis",
"pos": [
42,
57
],
"type": "Disease"
}
] | Overall , the establishment of a likely " hemochromatosis critical region " centromeric boundary and the identification of a linkage - disequilibrium zone both significantly contribute to a reduction in the amount of DNA required to be searched for novel coding sequences constituting the HFE defect |
[
{
"name": "tumor",
"pos": [
76,
81
],
"type": "Disease"
}
] | Genomic structure of the EWS gene and its relationship to EWSR1 , a site of tumor - associated chromosome translocation . |
[
{
"name": "Ewing sarcoma",
"pos": [
155,
168
],
"type": "Disease"
},
{
"name": "neuroectodermal tumors",
"pos": [
181,
203
],
"type": "Disease"
}
] | The EWS gene has been identified based on its location at the chromosome 22 breakpoint of the t ( 11 ; 22 ) ( q24 ; q12 ) translocation that characterizes Ewing sarcoma and related neuroectodermal tumors . |
[] | The EWS gene spans about 40 kb of DNA and is encoded by 17 exons . |
[] | The nucleotide sequence of the exons is identical to that of the previously described cDNA . |
[] | The first 7 exons encode the N - terminal domain of EWS , which consists of a repeated degenerated polypeptide of 7 to 12 residues rich in tyrosine , serine , threonine , glycine , and glutamine . |
[] | Exons 11 , 12 , and 13 encode the putative RNA binding domain . |
[] | The three glycine - and arginine - rich motifs of the gene are mainly encoded by exons 8 - 9 , 14 , and 16 . |
[] | The DNA sequence in the 5 region of the gene has features of a CpG - rich island and lacks canonical promoter elements , such as TATA and CCAAT consensus sequences . |
[
{
"name": "Ewing tumors",
"pos": [
66,
78
],
"type": "Disease"
}
] | Positions of the chromosome 22 breakpoints were determined for 19 Ewing tumors . |
[] | They were localized in introns 7 or 8 in 18 cases and in intron 10 in 1 case . . |
[
{
"name": "Norrie disease",
"pos": [
0,
14
],
"type": "Disease"
}
] | Norrie disease gene : characterization of deletions and possible function . |
[
{
"name": "Norrie disease",
"pos": [
95,
109
],
"type": "Disease"
},
{
"name": "pseudoglioma",
"pos": [
112,
124
],
"type": "Disease"
},
{
"name": "NDP",
"pos": [
127,
130
],
"type": "Disease"
},
{
"name": "X - linked neurodevelopmental disorder",
"pos": [
144,
182
],
"type": "Disease"
}
] | Positional cloning experiments have resulted recently in the isolation of a candidate gene for Norrie disease ( pseudoglioma ; NDP ) , a severe X - linked neurodevelopmental disorder . |
[
{
"name": "NDP",
"pos": [
87,
90
],
"type": "Disease"
}
] | Here we report the isolation and analysis of human genomic DNA clones encompassing the NDP gene . |
[] | The gene spans 28 kb and consists of 3 exons , the first of which is entirely contained within the 5 untranslated region . |
[
{
"name": "Norrie",
"pos": [
42,
48
],
"type": "Disease"
}
] | Detailed analysis of genomic deletions in Norrie patients shows that they are heterogeneous , both in size and in position . |
[
{
"name": "NDP",
"pos": [
50,
53
],
"type": "Disease"
}
] | By PCR analysis , we found that expression of the NDP gene was not confined to the eye or to the brain . |
[
{
"name": "NDP",
"pos": [
67,
70
],
"type": "Disease"
}
] | An extensive DNA and protein sequence comparison between the human NDP gene and related genes from the database revealed homology with cysteine - rich protein - binding domains of immediate - - early genes implicated in the regulation of cell proliferation . |
[] | We propose that NDP is a molecule related in function to these genes and may be involved in a pathway that regulates neural cell differentiation and proliferation . . |
[
{
"name": "Huntington disease",
"pos": [
11,
29
],
"type": "Disease"
},
{
"name": "HD",
"pos": [
32,
34
],
"type": "Disease"
},
{
"name": "HD",
"pos": [
100,
102
],
"type": "Disease"
}
] | The normal Huntington disease ( HD ) allele , or a closely linked gene , influences age at onset of HD . |
[
{
"name": "Huntington disease",
"pos": [
33,
51
],
"type": "Disease"
},
{
"name": "HD",
"pos": [
54,
56
],
"type": "Disease"
},
{
"name": "HD",
"pos": [
87,
89
],
"type": "Disease"
}
] | We evaluated the hypothesis that Huntington disease ( HD ) is influenced by the normal HD allele by comparing transmission patterns of genetically linked markers at the D4S10 locus in the normal parent against age at onset in the affected offspring . |
[] | Analysis of information from 21 sibships in 14 kindreds showed a significant tendency for sibs who have similar onset ages to share the same D4S10 allele from the normal parent . |
[] | Affected sibs who inherited different D4S10 alleles from the normal parent tended to have more variable ages at onset . |
[
{
"name": "HD",
"pos": [
46,
48
],
"type": "Disease"
},
{
"name": "HD",
"pos": [
76,
78
],
"type": "Disease"
}
] | These findings suggest that the expression of HD is modulated by the normal HD allele or by a closely linked locus . . |
[
{
"name": "Tay - Sachs disease",
"pos": [
108,
127
],
"type": "Disease"
}
] | Further investigation of the HEXA gene intron 9 donor splice site mutation frequently found in non - Jewish Tay - Sachs disease patients from the British Isles . |
[
{
"name": "Tay - Sachs disease",
"pos": [
36,
55
],
"type": "Disease"
},
{
"name": "TSD",
"pos": [
58,
61
],
"type": "Disease"
}
] | In a previous study we found that a Tay - Sachs disease ( TSD ) causing mutation in the intron 9 donor splice site of the HEXA gene occurs at high frequency in non - Jewish patients and carriers from the British Isles . |
[] | It was found more frequently in subjects of Irish , Scottish , and Welsh origin compared with English origin ( 63 % and 31 % respectively ) . |
[
{
"name": "TSD",
"pos": [
52,
55
],
"type": "Disease"
}
] | We have now tested , in a blind study , 26 American TSD carriers and 28 non - carriers who have British ancestry for the intron 9 splice site mutation . |
[] | Six of the carriers and none of the controls were positive for the mutation . |
[
{
"name": "TSD",
"pos": [
95,
98
],
"type": "Disease"
}
] | All six had Irish ancestry , compared with nine of the 20 other ( intron 9 mutation negative ) TSD carriers ( p < 0 . 05 ) . |
[
{
"name": "TSD",
"pos": [
99,
102
],
"type": "Disease"
}
] | These results confirm the previously found high frequency of the intron 9 mutation in non - Jewish TSD families of British Isles , particularly Irish , origin , and reinforce the need to screen such families for this mutation . |
[
{
"name": "tumors",
"pos": [
47,
53
],
"type": "Disease"
},
{
"name": "bilateral and unilateral retinoblastoma",
"pos": [
73,
112
],
"type": "Disease"
}
] | Molecular mechanisms of oncogenic mutations in tumors from patients with bilateral and unilateral retinoblastoma . |
[
{
"name": "retinoblastoma tumors",
"pos": [
27,
48
],
"type": "Disease"
}
] | The RB1 gene from 12 human retinoblastoma tumors has been analyzed exon - by - exon with the single - strand conformation polymorphism technique . |
[
{
"name": "tumors",
"pos": [
28,
34
],
"type": "Disease"
},
{
"name": "tumors",
"pos": [
60,
66
],
"type": "Disease"
}
] | Mutations were found in all tumors , and one - third of the tumors had independent mutations in both alleles neither of which were found in the germ line , confirming their true sporadic nature . |
[
{
"name": "tumors",
"pos": [
37,
43
],
"type": "Disease"
}
] | In the remaining two - thirds of the tumors only one mutation was found , consistent with the loss - of - heterozygosity theory of tumorigenesis . |
[] | Point mutations , the majority of which were C - - > T transitions , were the most common abnormality and usually resulted in the conversion of an arginine codon to a stop codon . |
[] | Small deletions were the second most common abnormality and most often created a downstream stop codon as the result of a reading frameshift . |
[] | Deletions and point mutations also affected splice junctions . |
[] | Direct repeats were present at the breakpoint junctions in the majority of deletions , supporting a slipped - mispairing mechanism . |
[] | Point mutations generally produced DNA sequences which resulted in perfect homology with endogenous sequences which lay within 14 bp . . |
[
{
"name": "aniridia",
"pos": [
18,
26
],
"type": "Disease"
}
] | PAX6 mutations in aniridia . |
[
{
"name": "Aniridia",
"pos": [
0,
8
],
"type": "Disease"
},
{
"name": "congenital malformation of the eye",
"pos": [
14,
48
],
"type": "Disease"
},
{
"name": "iris hypoplasia",
"pos": [
76,
91
],
"type": "Disease"
},
{
"name": "blindness",
"pos": [
110,
119
],
"type": "Disease"
}
] | Aniridia is a congenital malformation of the eye , chiefly characterised by iris hypoplasia , which can cause blindness . |
[
{
"name": "aniridia",
"pos": [
42,
50
],
"type": "Disease"
},
{
"name": "aniridia",
"pos": [
117,
125
],
"type": "Disease"
}
] | The PAX6 gene was isolated as a candidate aniridia gene by positional cloning from the smallest region of overlap of aniridia - associated deletions . |
[
{
"name": "aniridia",
"pos": [
115,
123
],
"type": "Disease"
},
{
"name": "aniridia",
"pos": [
140,
148
],
"type": "Disease"
}
] | Subsequently PAX6 intragenic mutations were demonstrated in Smalleye , a mouse mutant which is an animal model for aniridia , and six human aniridia patients . |
[
{
"name": "aniridia",
"pos": [
66,
74
],
"type": "Disease"
}
] | In this paper we describe four additional PAX6 point mutations in aniridia patients , both sporadic and familial . |
[] | These mutations highlight regions of the gene which are essential for normal PAX6 function . |
[
{
"name": "aniridia",
"pos": [
127,
135
],
"type": "Disease"
}
] | In addition , the frequency at which we have found PAX6 mutations suggests that lesions in PAX6 will account for most cases of aniridia . . |
[] | Detection of a novel arginine vasopressin defect by dideoxy fingerprinting . |
[
{
"name": "Autosomal dominant neurohypophyseal diabetes insipidus",
"pos": [
0,
54
],
"type": "Disease"
},
{
"name": "diabetes insipidus",
"pos": [
77,
95
],
"type": "Disease"
}
] | Autosomal dominant neurohypophyseal diabetes insipidus is a familial form of diabetes insipidus . |
[
{
"name": "diabetes insipidus",
"pos": [
85,
103
],
"type": "Disease"
}
] | This disorder is associated with variable levels of arginine vasopressin ( AVP ) and diabetes insipidus of varying severity , which responds to exogenous AVP . |
[
{
"name": "autosomal dominant neurohypophyseal diabetes insipidus",
"pos": [
36,
90
],
"type": "Disease"
}
] | To determine the molecular basis of autosomal dominant neurohypophyseal diabetes insipidus , the AVP genes of members of a large kindred were analyzed . |