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Clinical Trial
. 2003 Feb;87(2):197-202.
doi: 10.1136/bjo.87.2.197.

A clinical and molecular genetic study of a rare dominantly inherited syndrome (MRCS) comprising of microcornea, rod-cone dystrophy, cataract, and posterior staphyloma

M A Reddy  1 , P J Francis, V Berry, K Bradshaw, R J Patel, E R Maher, R Kumar, S S Bhattacharya, A T Moore
Affiliations
Clinical Trial

A clinical and molecular genetic study of a rare dominantly inherited syndrome (MRCS) comprising of microcornea, rod-cone dystrophy, cataract, and posterior staphyloma

M A Reddy et al. Br J Ophthalmol. 2003 Feb.

Abstract

Aim: To phenotype and genetically map the disease locus in a family presenting with autosomal dominant microcornea, rod-cone dystrophy, cataract, and posterior staphyloma.

Methods: Six affected and three unaffected members of the pedigree were examined. All individuals provided a history and underwent a full clinical examination with A-scan and B-scan ultrasonography and electrophysiological testing where appropriate. PCR based microsatellite marker genotyping using a positional candidate gene approach was then performed on DNA samples extracted from venous blood provided by each subject.

Results: The disorder is inherited as an autosomal dominant trait with variable expressivity and has a complex phenotype. Affected individuals had bilateral microcornea, pulverulent-like lens opacities, a rod-cone dystrophy and posterior staphyloma (MRCS). Using a positional candidate gene approach, the authors have evidence suggestive of linkage of this disorder to a region on 11q13 within the nanophthalmos 1 (NNO1) genetic interval. The small family size militates against achieving a LOD score of 3, but the haplotype data and the position of the putative MRCS locus within a known nanophthalmos locus are suggestive of linkage. A candidate gene within this region (ROM1) was screened and no mutations were found in affected members of the family.

Conclusion: This rare developmental disorder has some phenotypic similarities to nanophthalmos and possibly maps to a locus within the genetic interval encompassing the NNO1 locus. Screening of candidate genes within this region continues.

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Figures

Figure 1
Figure 1
Family pedigree and haplotype analysis using microsatellite markers on 11q13. Affected individuals are denoted by solid symbols.
Figure 2
Figure 2
(A) and (B) Microcornea in individual II5. (C) Left inferonasal peripheral fundal view in individual IV1 showing demarcation line. (D) The right posterior pole in individual II:7 with arrow depicting the optic disc. (E) Oblique longitudinal ultrasound section demonstrating the posterior staphyloma in the left eye (individual II:5) SUP = superior, INF = inferior, POST = posterior, A = anterior.
Figure 3
Figure 3
Flash ERGs. Left panel: control; middle panel: patient IV:1; right panel: patient II:7. LA = light adapted. DA = dark adapted. SF = standard flash (ISCEV protocol, see text). OPs = oscillatory potentials. The vertical broken line indicates stimulus onset.
Figure 4
Figure 4
Schematic diagram of chromosome 11 indicating the provisional position of the MRCS in relation to the NNO1 locus. The microsatellite markers shown are those that form the haplotypes in Figure 1. The horizontal arrows indicate the boundaries of the critical genetic interval for MRCS on 11q13 as defined by recombination events.
See this image and copyright information in PMC

References

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