PURPOSE: 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.
PURPOSE: 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.
Authors: Owen M Siggs; Shari Javadiyan; Shiwani Sharma; Emmanuelle Souzeau; Karen M Lower; Deepa A Taranath; Jo Black; John Pater; John G Willoughby; Kathryn P Burdon; Jamie E Craig Journal: Eur J Hum Genet Date: 2017-03-08 Impact factor: 4.246
Authors: Kamron Khan; Adam Rudkin; David A Parry; Kathryn P Burdon; Martin McKibbin; Clare V Logan; Zakia I A Abdelhamed; James S Muecke; Narcis Fernandez-Fuentes; Kate J Laurie; Mike Shires; Rhys Fogarty; Ian M Carr; James A Poulter; Joanne E Morgan; Moin D Mohamed; Hussain Jafri; Yasmin Raashid; Ngy Meng; Horm Piseth; Carmel Toomes; Robert J Casson; Graham R Taylor; Michael Hammerton; Eamonn Sheridan; Colin A Johnson; Chris F Inglehearn; Jamie E Craig; Manir Ali Journal: Am J Hum Genet Date: 2011-09-09 Impact factor: 11.025