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.
|Number of pages||7|
|Publication status||Published - 08 Aug 2005|
ASJC Scopus subject areas
Willoughby, C., Heon, E., Chandna, A., Mok, C., Shafiq, A., Ferrini, W., Chan, L. L. Y., Billingsley, G., Priston, M., & Kaye, S. (2005). CRYBB1 mutation associated with congenital cataract and microcornea. Molecular Vision, 11, 587-593.