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


CONCLUSIONS
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.
Reddy
M A
MA
Institute of Ophthalmology, London, UK. mareddy@doctors.org.uk
Francis
P J
PJ
Berry
V
V
Bradshaw
K
K
Patel
R J
RJ
Maher
E R
ER
Kumar
R
R
Bhattacharya
S S
SS
Moore
A T
AT
D000293:Adolescent; D000328:Adult; D002386:Cataract / Q000235:genetics*; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics*; D003315:Cornea / Q000002:abnormalities*; D004247:DNA / Q000032:analysis; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics*; D015422:Scleral Diseases / Q000235:genetics*; D013577:Syndrome
D005819:Genetic Markers; D004247:DNA