CRYBB1 mutation associated with congenital cataract and microcornea.
OBJECTIVE
The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported.


METHODS
Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing.


RESULTS
Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls.


CONCLUSIONS
X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.
Willoughby
Colin E
CE
Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Canada. c.willoughby@qub.ac.uk
Shafiq
Ayad
A
Ferrini
Walter
W
Chan
Louie Loh Yen
LL
Billingsley
Gail
G
Priston
Megan
M
Mok
Calvin
C
Chandna
Arvind
A
Kaye
Stephen
S
Héon
Elise
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D002386:Cataract / Q000151:congenital*; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003315:Cornea / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D038206:beta-Crystallin B Chain / Q000235:genetics*
C105601:CRYBB1 protein, human; D038206:beta-Crystallin B Chain