Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A new locus for autosomal dominant familial exudative vitreoretinopathy maps to chromosome 11p12-13.

ABSTRACT: We report a new locus for familial exudative vitreoretinopathy (FEVR), on chromosome 11p12-13 in a large autosomal dominant pedigree. Statistically significant linkage was achieved across a 14-cM interval flanked by markers GATA34E08 and D11S4102, with a maximum multipoint LOD score of 6.6 at D11S2010. FEVR is a disease characterized by the failure of development of peripheral retinal blood vessels, and it is difficult to diagnose clinically because of the wide spectrum of fundus abnormalities associated with it. The identification of a new locus is important for genetic counseling and potentiates further studies aimed toward the identification of a gene with an important role in angiogenesis within neuroepithelial tissues. Such a gene may also have a role in the genetic predisposition to retinopathy of prematurity, a sporadic disorder with many clinical similarities to FEVR.

SUBMITTER: Downey LM

PROVIDER: S-EPMC1274490 | biostudies-literature | 2001 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A new locus for autosomal dominant familial exudative vitreoretinopathy maps to chromosome 11p12-13.

Downey L M LM Keen T J TJ Roberts E E Mansfield D C DC Bamashmus M M Inglehearn C F CF

American journal of human genetics 20010119 3

We report a new locus for familial exudative vitreoretinopathy (FEVR), on chromosome 11p12-13 in a large autosomal dominant pedigree. Statistically significant linkage was achieved across a 14-cM interval flanked by markers GATA34E08 and D11S4102, with a maximum multipoint LOD score of 6.6 at D11S2010. FEVR is a disease characterized by the failure of development of peripheral retinal blood vessels, and it is difficult to diagnose clinically because of the wide spectrum of fundus abnormalities a ...[more]

PMID: 11179025

Similar Datasets

Mutations in TSPAN12 cause autosomal-dominant familial exudative vitreoretinopathy.

Project description:Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Although mutations in three genes (LRP5, FZD4, and NDP) are known to cause FEVR, these account for only a fraction of FEVR cases. The proteins encoded by these FEVR genes form part of a signaling complex that activates the Norrin-beta-catenin signaling pathway. Recently, through a large-scale reverse genetic screen in mice, Junge and colleagues identified an additional member of this signaling complex, Tspan12. Here, we report that mutations in TSPAN12 also cause autosomal-dominant FEVR. We describe seven mutations identified in a cohort of 70 FEVR patients in whom we had already excluded the known FEVR genes. This study provides further evidence for the importance of the Norrin-beta-catenin signaling pathway in the development of the retinal vasculature and also indicates that more FEVR genes remain to be identified.

| S-EPMC2820188 | biostudies-literature

A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

Project description:Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4.

| S-EPMC1377876 | biostudies-literature

Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.

Project description:Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Autosomal dominant FEVR is genetically heterogeneous, but its principal locus, EVR1, is on chromosome 11q13-q23. The gene encoding the Wnt receptor frizzled-4 (FZD4) was recently reported to be the EVR1 gene, but our mutation screen revealed fewer patients harboring mutations than expected. Here, we describe mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor. This finding further underlines the significance of Wnt signaling in the vascularization of the eye and highlights the potential dangers of using multiple families to refine genetic intervals in gene-identification studies.

| S-EPMC1181948 | biostudies-literature

An SNX31 variant underlies dominant familial exudative vitreoretinopathy-like pathogenesis.

Project description:Familial exudative vitreoretinopathy (FEVR) is a complex hereditary eye disorder characterized by incomplete development of the retinal vasculature, which thereby affects retinal angiogenesis. But the genetic factors contributing to FEVR's development or pathogenesis remain elusive. In a Chinese family with FEVR with 19 members, by using whole-exome sequencing, we identified a candidate disease-causing DNA variant in sorting nexin 31 (SNX31) (c.963delG; p. Trp321Cys), which results in a frameshift mutation. We studied the biochemical mechanism of this mutation and determined that it is deficient in β1-integrin binding and stability. The SNX31 c.963delG point mutation mouse model (SNX31m/m) was constructed with CRISPR/Cas9 technology. At 2-4 months of age, SNX31m/m mice showed fundus phenotypes similar to FEVR-like changes, including vascular leakage and retinal atrophy. Moreover, we found that VEGF and apoptotic pathways were involved in these ocular phenotypes. Hence, our study extended the FEVR mutation spectrum to include SNX31. These findings expanded our understanding of the molecular pathogenesis of FEVR and may facilitate the development of methods for the diagnosis and prevention of FEVR.

| S-EPMC10322688 | biostudies-literature

A new susceptibility locus for autosomal dominant pancreatic cancer maps to chromosome 4q32-34.

Project description:Pancreatic cancer is the fifth leading cause of cancer death in the United States. Nearly every person diagnosed with pancreatic cancer will die from it, usually in <6 mo. Familial clustering of pancreatic cancers is commonly recognized, with an autosomal dominant inheritance pattern in approximately 10% of all cases. However, the late age at disease onset and rapid demise of affected individuals markedly hamper collection of biological samples. We report a genetic linkage scan of family X with an autosomal dominant pancreatic cancer with early onset and high penetrance. For the study of this family, we have developed an endoscopic surveillance program that allows the early detection of cancer and its precursor, before family members have died of the disease. In a genomewide screening of 373 microsatellite markers, we found significant linkage (maximum LOD score 4.56 in two-point analysis and 5.36 in three-point analysis) on chromosome 4q32-34, providing evidence for a major locus for pancreatic cancer.

| S-EPMC379100 | biostudies-literature

A new locus for autosomal dominant intracranial aneurysm, ANIB4, maps to chromosome 5p15.2-14.3.

Project description:BackgroundIntracranial aneurysms (IA) are dilatations of intracranial arteries that occur most commonly at arterial bifurcations. Unruptured IA are present in approximately 1-2% of the population aged over 30 years of age. Aneurysms are only rarely symptomatic unless they rupture, which typically results in a subarachnoid haemorrhage associated with high morbidity and mortality.MethodsA large French Canadian (FC) family (Aneu60) was identified which contained 12 affected individuals with intracranial aneurysms. Nine of the affected patients and three unaffected individuals were sent for an 8 cM genome-wide scan. Multipoint and two-point methods were used to analyse the scan data by using a dominant parametric model.ResultsWe identified an IA susceptibility locus (ANIB4) located on chromosome 5p15.2-14.3. The locus was found by genome-wide linkage analysis and follow up analyses provided a maximum multipoint LOD score of 3.57 over the region. An identical haplotype segment of 7.2 Mb was found in a second FC pedigree and contributes to the refinement of the candidate gene interval.ConclusionsOur results indicate that there is a major gene locus on chromosome 5p.

| S-EPMC2564548 | biostudies-literature

Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.

Project description:Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus-directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314. The maximum LOD score of 3.6 at theta =0 is obtained with marker D11S987. Haplotype analysis confirms that the critical region is the 22-cM (311-Mb) interval flanked by markers D11S905 and D11S1314. This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR. Sequencing of LRP5 shows, in all three families, homozygous mutations R570Q, R752G, and E1367K. This suggests that mutations in this gene can cause autosomal recessive as well as autosomal dominant FEVR.

| S-EPMC1182117 | biostudies-literature

A locus for autosomal dominant colobomatous microphthalmia maps to chromosome 15q12-q15.

Project description:Congenital microphthalmia is a common developmental ocular disorder characterized by shortened axial length. Isolated microphthalmia is clinically and genetically heterogeneous and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Here, we studied a five-generation family of Sephardic Jewish origin that included 38 members, of whom 7 have either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. After exclusion of several candidate loci, we performed a genome-scan study and demonstrated linkage to chromosome 15q12-q15. Positive LOD scores were obtained with a maximum at the D15S1007 locus (maximum LOD score 3.77, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene in a 13.8-cM interval between loci D15S1002 and D15S1040.

| S-EPMC1287937 | biostudies-literature

A new locus for autosomal dominant posterior polar cataract in Moroccan Jews maps to chromosome 14q22-23.

Project description:BackgroundPosterior polar cataract is a clinically distinctive opacity located at the back of the lens. It is commonly acquired in age related cataract, and may infrequently occur in pedigrees with congenital cataract. To date, five loci for autosomal dominant congenital posterior polar cataract have been identified. These include two genes, CRYAB and PITX3, on chromosomes 11q and 10q respectively, and three loci with as yet unknown genes on chromosomes 1p, 16q and 20p.PurposeTo find the chromosomal location of a gene causing autosomal dominant congenital posterior polar cataract in three Moroccan Jewish families.MethodsA whole genome scan was performed using microsatellite markers spaced at approximately 10 cM intervals. For fine mapping, five additional microsatellite markers were genotyped. Two-point lod scores were calculated using MLINK software, from the LINKAGE program package. After linkage was established, several positional candidate genes were assessed by PCR based DNA sequencing.ResultsThe new cataract locus was mapped to an 11.3 cM interval between D14S980 and D14S1069 on chromosome 14q22-23. A maximum two point lod score of 5.19 at theta = 0 was obtained with the markersD14S274. The positional and functional candidate genes SIX1, SIX4, SIX6, OTX2, and ARHJ were excluded as the cause of cataract in these families.ConclusionAn as yet unidentified gene associated with posterior polar cataract maps to the long arm of chromosome 14q22-23.

| S-EPMC2563169 | biostudies-literature

A locus for autosomal dominant "pure" hereditary spastic paraplegia maps to chromosome 19q13.

Project description:Genetic loci for autosomal dominant pure hereditary spastic paraplegia (ADPHSP) have been mapped to chromosomes 2p, 8q, 12q, 14q, and 15q. We undertook a genomewide linkage screen of a large family with ADPHSP, for which linkage at all previously identified ADPHSP loci was excluded. Analysis of markers on chromosome 19q gave a peak pairwise LOD score of 3.72 at D19S420, allowing assignment of a novel ADPHSP locus (which we have termed "SPG12") to this region. Haplotype construction and analysis of recombination events narrowed the SPG12 locus to a 16.1-cM region between markers D19S868 and D19S902.

| S-EPMC1288126 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data