A mutation in GJA8 (p.P88Q) is associated with "balloon-like" cataract with Y-sutural opacities in a family of Indian origin.
OBJECTIVE
To detect the underlying genetic defect in a family with three members in two generations affected with bilateral congenital cataract.


METHODS
Detailed family history and clinical data were recorded. Mutation screening in the candidate genes, alphaA-crystallin (CRYAA), betaA1-crystallin (CRYBA1), betaB2-crystallin (CRYBB2), gammaA-gammaD-crystallins (CRYGA, CRYGB, CRYGC, and CRYGD), connexin-46 (GJA3), and connexin-50 (GJA8), was performed by bidirectional sequencing of the amplified products.


RESULTS
Affected individuals had "balloon-like" cataract with prominent Y-sutural opacities. Sequencing of the candidate genes showed a heterozygous c.262C>A change in the gene for connexin 50 (GJA8), which is localized at 1q21, that resulted in the replacement of a highly conserved proline by glutamine (p.P88Q). This sequence change was not observed in 96 ethnically matched controls.


CONCLUSIONS
We report a p.P88Q mutation in GJA8 associated with Y-sutural cataract in a family of Indian origin. Mutations of the same codon have previously been described in British families with pulverulent cataract, suggesting that modifying factors may determine the type of cataract.
Vanita
Vanita
V
Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India. vanita_kumar@yahoo.com
Singh
Jai Rup
JR
Singh
Daljit
D
Varon
Raymonda
R
Sperling
Karl
K
D019943:Amino Acid Substitution; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002648:Child; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007194:India / Q000208:ethnology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011392:Proline / Q000235:genetics; D006113:United Kingdom; D000099264:Connexin 50
D017630:Connexins; D005136:Eye Proteins; D005973:Glutamine; D011392:Proline; D000099264:Connexin 50