Autosomal dominant (AD)
Information on the inheritance of FEVR.
Autosomal dominant (AD) is the most common form of inheritance of FEVR. The frizzled-4 gene was recently discovered in 11q chromosome as one of the genes that cause AD FEVR. Another locus for AD disease is in 11p, the gene is still unknown. It is quite possible that few other unknown yet genes might cause AD FEVR.
The second most common form of tranmsmission is x-linked. Patients with the x-linked form have quite often mutations in the Norrie disease gene. It is quite possible also that this type of FEVR could also be caused by other genes as well.
A third type of inheritance is autosomal recessive, it is the least common and genes are still unknown.
|Nat Genet 2002 Oct;32(2):326-30||Related Articles, Links|
Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.
Robitaille J, MacDonald ML, Kaykas A, Sheldahl LC, Zeisler J, Dube MP, Zhang LH, Singaraja RR, Guernsey DL, Zheng B, Siebert LF, Hoskin-Mott A, Trese MT, Pimstone SN, Shastry BS, Moon RT, Hayden MR, Goldberg YP, Samuels ME.
Department of Ophthalmology, Izaak Walton Killam (IWK) Health Centre, Dalhousie University, Halifax, Nova Scotia B3H 2Y9, Canada.
Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Loci associated with FEVR map to 11q13-q23 (EVR1; OMIM 133780, ref. 1), Xp11.4 (EVR2; OMIM 305390, ref. 2) and 11p13-12 (EVR3; OMIM 605750, ref. 3). Here we have confirmed linkage to the 11q13-23 locus for autosomal dominant FEVR in one large multigenerational family and refined the disease locus to a genomic region spanning 1.55 Mb. Mutations in FZD4, encoding the putative Wnt receptor frizzled-4, segregated completely with affected individuals in the family and were detected in affected individuals from an additional unrelated family, but not in normal controls. FZD genes encode Wnt receptors, which are implicated in development and carcinogenesis. Injection of wildtype and mutated FZD4 into Xenopus laevis embryos revealed that wildtype, but not mutant, frizzled-4 activated calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway. In one of the mutants, altered subcellular trafficking led to defective signaling. These findings support a function for frizzled-4 in retinal angiogenesis and establish the first association between a Wnt receptor and human disease.
PMID: 12172548 [PubMed – indexed for MEDLINE]
|Hum Genet 2001 May;108(5):368-75||Related Articles, Links|
Delineation of the critical interval for the familial exudative vitreoretinopathy gene by linkage and haplotype analysis.
Kondo H, Ohno K, Tahira T, Hayashi H, Oshima K, Hayashi K.
Division of Genome Analysis, Kyushu University, Fukuoka, Japan.
Familial exudative vitreoretinopathy (FEVR) is an ocular disorder characterized by deficient vascularization of the peripheral retina and causes visual loss attributable to various types of retinal detachment. The locus of the gene responsible for the autosomal dominant form of FEVR (EVR1) has been assigned to 11q13-23. However, a detailed evaluation of the critical region has not been made. We present the results of linkage analysis of the EVR1 locus on 11q13-23 in 43 individuals belonging to seven unrelated families of Japanese origin. Multipoint analysis has shown that six families out of the seven are linked with 11q13-23 markers. Haplotype analysis reveals that the putative region is probably flanked by polymorphic markers D11S1362 and CHLC.GATA30G01, which are approximately 200 kb apart, although the recombination events in small families such as presented in this study should be interpreted cautiously.
PMID: 11409862 [PubMed – indexed for MEDLINE]
|Am J Hum Genet 2001 Mar;68(3):778-81||Related Articles, Links|
A new locus for autosomal dominant familial exudative vitreoretinopathy maps to chromosome 11p12-13.
Downey LM, Keen TJ, Roberts E, Mansfield DC, Bamashmus M, Inglehearn CF.
Molecular Medicine Unit, Saint James’s University Hospital, Leeds, LS9 7TF, United Kingdom.
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.
PMID: 11179025 [PubMed – indexed for MEDLINE]
|Clin Genet 2000 Oct;58(4):329-32||Related Articles, Links|
Linkage and candidate gene analysis of autosomal-dominant familial exudative vitreoretinopathy.
Shastry BS, Hejtmancik JF, Hiraoka M, Ibaraki N, Okubo Y, Okubo A, Han DP, Trese MT.
PMID: 11076059 [PubMed – indexed for MEDLINE]
|Br J Ophthalmol 2000 Apr;84(4):358-63||Related Articles, Links|
Genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of the EVR1 locus on chromosome 11q in a large autosomal dominant pedigree.
(FULL TEXT AVALIABLE)
Bamashmus MA, Downey LM, Inglehearn CF, Gupta SR, Mansfield DC.
Molecular Medicine Unit, CSB, St James’s University Hospital, Leeds University, Leeds, UK.
BACKGROUND/AIMS: Familial exudative vitreoretinopathy (FEVR) is associated with mutations in the Norrie disease gene in X linked pedigrees and with linkage to the EVR1 locus at 11q13 in autosomal dominant cases. A large autosomal dominant FEVR family was studied, both clinically and by linkage analysis, to determine whether it differed from the known forms of FEVR. METHODS: Affected members and obligate gene carriers from this family were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and in some cases fluorescein angiography. Patient DNAs were genotyped for markers at the EVR1 locus on chromosome 11q13. RESULTS: The clinical evaluation in this family is consistent with previous descriptions of FEVR pedigrees, but linkage analysis proves that it has a form of FEVR genetically distinct from the EVR1 locus on 11q. CONCLUSION: This proves that there are at least three different loci associated with comparable FEVR phenotypes, a situation similar to that existing for many forms of retinal degeneration.
PMID: 10729291 [PubMed – indexed for MEDLINE]
|Ophthalmic Genet 1996 Jun;17(2):53-7||Related Articles, Links|
Familial exudative vitreoretinopathy linked to D11S533 in a large Asian family with consanguinity.
Price SM, Periam N, Humphries A, Woodruff G, Trembath RC.
Department of Clinical Genetics, Leicester Royal Infirmary, UK.
Familial exudative vitreoretinopathy (FEVR) is a disorder characterised by peripheral retinal vascularisation with subsequent traction of retinal vessels and detachment. Recently, autosomal dominant FEVR (ad FEVR) has been mapped to 11q13 by linkage in four northern European families. We describe a large consanguineous Asian family in which the severity of the proband’s eye disease suggested homozygosity for a disease allele. Thirty family members were assessed by ophthalmological examination and fluorescein angiography. Thirteen had unequivocal features of FEVR. A further two were classified as unknown. Two point linkage analysis for DIIS533 and FEVR generated a lod score of 5.55 at a recombination fraction of 0.00. This supports autosomal dominant inheritance and demonstrates genetic homogeneity for the ad FEVR disease locus. The severely affected proband was heterozygous for alleles at this closely linked locus. Other causes, including non-genetic factors, should be considered to explain the extreme variability characteristic of ad FEVR.
PMID: 8832721 [PubMed – indexed for MEDLINE]
|J Fr Ophtalmol 1995;18(3):231-7||Related Articles, Links|
[Familial exudative vitreoretinopathy and hereditary retinal vascular tortuosity]
[Article in French]
Khairallah M, Belaiba A, Aloulou K, Chachia N.
Service d’Ophtalmologie, C.H.U. Fattouma Bourguiba, Monastir, Tunisie.
PURPOSE: A 9 year-old child demonstrated symptomatic exudative vitreoretinopathy. The other family members were examined to detect funduscopic changes suggestive of the disease. METHODS: A complete ocular examination was performed including fundus biomicroscopic examination and fluorescein angiography. RESULTS: The patient with exudative vitreoretinopathy exhibited retinal neovascularisation and minime vitreous hemorrhage in one eye. He was successfully treated with laser photocoagulation. The mother and her 5 other children had isolated retinal vascular tortuosity. CONCLUSION: The association in the same pedigree of exudative vitreoretinopathy and retinal vascular tortuosity suggest the same nosologic frame to these autosomal dominant diseases. They could represent different expressions of the same genetic disorder.
PMID: 7759764 [PubMed – indexed for MEDLINE]
|Am J Hum Genet 1992 Oct;51(4):749-54||Links|
The autosomal dominant familial exudative vitreoretinopathy locus maps on 11q and is closely linked to D11S533.
Li Y, Muller B, Fuhrmann C, van Nouhuys CE, Laqua H, Humphries P, Schwinger E, Gal A.
Institut fur Humangenetik, Medizinische Universitat, Lubeck, Germany.
Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is a hereditary disorder characterized by the incomplete vascularization of the peripheral retina. The primary biochemical defect in adFEVR is unknown. The adFEVR locus has tentatively been assigned to 11q by linkage studies. We report the results of an extended multipoint linkage analysis of two families with adFEVR by using five markers (INT2, D11S533, D11S527, D11S35, and CD3D) from 11q13-q23. Pairwise linkage data obtained in the two families were rather similar and hence have not provided evidence for genetic heterogeneity. The highest complied two-point lod score (3.67, at a recombination fraction of .07) was obtained for the disease locus versus D11S533. Multipoint analyses showed that the adFEVR locus maps most likely, with a maximum location score of over 20, between D11S533/D11S527 and D11S35, at recombination rates of .147 and .104, respectively. Close linkage without recombination (maximum lod score 11.26) has been found between D11S533 and D11S527.
PMID: 1415220 [PubMed – indexed for MEDLINE]
|Am J Ophthalmol 1992 Jun 15;113(6):712-3||Related Articles, Links|
The gene for autosomal dominant familial exudative vitreoretinopathy (Criswick-Schepens) on the long arm of chromosome 11.
Li Y, Fuhrmann C, Schwinger E, Gal A, Laqua H.
PMID: 1598965 [PubMed – indexed for MEDLINE]