A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family.
OBJECTIVE
The molecular characterization of an Indian family having 10 members in four generations affected with a unique fan-shaped cataract-microcornea syndrome.


METHODS
Detailed family history and clinical data were recorded. A genome-wide screening by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bi-directional sequencing of amplified products.


RESULTS
The cataract-microcornea locus in this family was mapped to a 23.5 cM region on chromosome 21q22.3. Direct sequencing of the candidate gene CRYAA revealed a heterozygous C>T transition resulting in the substitution of the highly conserved arginine at position 116 by cysteine (R116C).


CONCLUSIONS
This study provides the report of mapping a locus for syndromal cataract (cataract-microcornea syndrome) on 21q22.3. The mutation observed in CRYAA in the present family highlights the phenotypic heterogeneity of the disorder in relation to the genotype, as an identical mutation has previously been reported in an American family with a different type of cataract. The "fan-shaped cataract" observed in the present family has not been reported before.
Vanita
Vanita
V
Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, Punjab, India. vanita_kumar@yahoo.com
Singh
Jai Rup
JR
Hejtmancik
James Fielding
JF
Nuernberg
Peter
P
Hennies
Hans Christian
HC
Singh
Daljit
D
Sperling
Karl
K
D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D003315:Cornea / Q000002:abnormalities* / Q000473:pathology; D003459:Crystallins / Q000235:genetics*; D003596:Cytosine; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007194:India; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D013577:Syndrome; D013941:Thymine
C511246:CRYAA protein, human; D003459:Crystallins; D003596:Cytosine; D013941:Thymine