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. 2000 Apr;84(4):358–363. doi: 10.1136/bjo.84.4.358

Genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of the EVR1 locus on chromosome 11q in a large autosomal dominant pedigree

M Bamashmus 1, L Downey 1, C Inglehearn 1, S Gupta 1, D Mansfield 1
PMCID: PMC1723437  PMID: 10729291

Abstract

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.



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Figure 1  .

Figure 1  

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The pedigree of the familial exudative vitreoretinopathy (FEVR) family described, segregating autosomal dominant FEVR, drawn using the program CYRILLIC 2. (A) A complete family tree, but many of the apparently normal individuals have not been examined by an ophthalmologist and the subtle nature of the FEVR phenotype in some cases is such that carrier status cannot be excluded. Solid symbols are confirmed as affected by clinical examination, those marked with a vertical line are said to be or to have been affected, those marked with a dot are asymptomatic obligate carriers, and those marked with a question mark have an uncertain diagnosis which is being investigated further. (B) A subset of (A) which has been subject to genetic analysis, and haplotypes for 11q markers are given below each symbol (reading downwards the haplotypes are obtained from markers D11S916, D11S527, D11S937, D11S1396, D11SS873, and D11S876). Affected individuals are also numbered (italic) to correspond with (A) and with Table 1.

Figure 2  .

Figure 2  

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Fundus photographs of the left and right eyes of the proband. (A) Right eye: temporal periphery shows white preretinal mass with retinal traction. This eye has previously undergone a pars plana vitrectomy together with endophotocoagulation (the scars from which can also be seen here). (B) Left eye: distortion of major retinal vessels at the optic disc due to vitreoretinal traction.

Figure 3  .

Figure 3  

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Multipoint lod scores from two separate analyses carried out on data from this pedigree, using the program LINKMAP, from the LINKAGE suit of programs. Penetrance was assumed to be 80% to allow for the possibility that some apparently normal individuals might in fact be carriers. The first analysis (points for which are marked as solid squares) used data from markers D11S916, D11S937, and D11S1396 against disease status. The second, which overlaps the first and is marked as a series of open circles, uses data from D11S1396, D11S873, and D11S876. Approximate positions of the EVR1 FEVR locus and the VRN1 ADNIV locus are shown above. Distances are a composite of those derived from several mapping sources.12 13 24 27-29 Genetic distances along the Y axis are given in centimorgans (cM) from marker D11S916.

Selected References

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