Autosomal dominant (AD)
Information on the inheritance
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, check 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
A third type of inheritance is autosomal recessive, order
it is the least common
and genes are still unknown.
HYPERTEXT OF DISEASE.
© 1991-2003, Pathology Informatics, Inc
Mutant frizzled-4 disrupts retinal angiogenesis in familial
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]
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]
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,
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]
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,
PMID: 11076059 [PubMed – indexed for MEDLINE]
Genetic heterogeneity in familial exudative vitreoretinopathy;
exclusion of the EVR1 locus on chromosome 11q in a large autosomal dominant
(FULL TEXT AVALIABLE)
Bamashmus MA, Downey LM, Inglehearn CF, Gupta SR, Mansfield DC.
Molecular Medicine Unit, CSB, St James’s University Hospital, Leeds University,
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
PMID: 10729291 [PubMed – indexed for MEDLINE]
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]
[Familial exudative vitreoretinopathy and hereditary retinal
[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]
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.
|Am J Hum Genet 1992 Oct;51(4):749-54
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
PMID: 1415220 [PubMed – indexed for MEDLINE]
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]