Purpose: To report and identify the genetic defect that causes progressive polymorphic congenital cataracts affecting a large five generation Chinese family.
Methods: Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. Genetic linkage analysis was performed on the known genetic loci for autosomal dominant congenital cataract (ADCC) with 41 short tandem repeat polymorphic markers. Mutations were screened by DNA sequencing and restriction fragment length analysis (RFLP).
Results: A significant two point LOD score was generated at marker D22S420, D22S539 and D22S315 for 22q11.2. The highest observed LOD score was 6.26 (theta=0.00) with marker D22S315. Mutation screening of the CRYBB2 gene in this family revealed an C-->T transition at position 475 (Q155X) of the cDNA sequence, creating a novel SpeI restriction site that cosegregated with affected members of the pedigree, but was not present in unaffected members or any of the 100 unrelated individuals tested.
Conclusions: Our finding expands the spectrum of cataract phenotypes caused by the Q155X mutation of CRYBB2, confirms the phenotypic heterogeneity of this mutation and suggests the mechanism that influences the congenital cataract formation in different ethnic backgrounds.