A Novel Form of “Central Pouchlike” Cataract, with Sutural Opacities, Maps to Chromosome 15q21-22

Abstract

Congenital cataract is a clinically and genetically highly heterogeneous eye disorder, with autosomal dominant inheritance being most common. We investigated a large seven-generation family with 74 individuals affected by autosomal dominant congenital cataract (ADCC). The phenotype in this family can be described as "central pouchlike" cataract with sutural opacities, and it differs from the other mapped cataracts. We performed linkage analysis with microsatellite markers in this family and excluded the known candidate genes. A genomewide search revealed linkage to markers on chromosome 15, with a maximum two-point LOD score of 5.98 at straight theta=0 with marker D15S117. Multipoint analysis also gave a maximum LOD score of 5.98 at D15S117. Multipoint and haplotype analysis narrowed the cataract locus to a 10-cM region between markers D15S209 and D15S1036, closely linked to marker D15S117 in q21-q22 region of chromosome 15. This is the first report of a gene for a clinically new type of ADCC at 15q21-22 locus.

Crystallins, genes and cataract

“…This mutation truncates CRYBB2 by 51 amino acids. The mutation Q155X is detectable in three geographically distinct pedigrees, American [284], Swiss [285] and East Indian [286], each with a morphologically different phenotype. If these proteins had merely a structural role, there probably would not be any heterogeneity in the phenotype.…”

A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance

“…These include genes for seven members of the crystallin family, 1 2 which are responsible for the refractive index and transparency of the lens, two connexin genes 3 4 and major intrinsic protein of the lens (MIP) 5 which are involved in the transport directly between cells of small metabolites and water, respectively, the cytoskeletal protein beaded filament structural protein-2 (BFSP2), 6 and transcription factors paired-like homeodomain transcription factor-3 (PITX3) 7 and heat shock factor-4 (HSF4). 8 Five additional loci have been described on chromosomes 1pter-p36.1, 9 15q21-q22, 10 17p13, 11 17q24, 12 and 20p12-q12. 13 We used a linkage approach to investigate these 13 genes and five loci in a large pedigree from Victoria, Australia, with zonular pulverulent cataract with the aim of identifying the causative mutation.…”

A novel locus of coralliform cataract mapped to chromosome 2p24-pter

“…At least seventeen loci of autosomal dominant congenital cataract (ADCC) have been mapped by linkage analysis on 13 human chromosomes. These loci are: 1p36 (Eiberg et al 1995;Ionides et al 1997), 1q21-q25 (Renwick and Lawler 1963), 2p12 (Khaliq et al 2002), 2q33-q35 (Lubsen et al 1987;Rogaev et al 1996), 3q21-q22 (Jakobs et al 2000), 10q24-q25 (Semina et al 1998), 11q22.3-q23.1 (Berry et al 2001), 12q13 (Bateman et al 2000), 13cen-q13 ), 15q21-q22 (Vanita et al 2001), 16q22.1 (Eiberg et al 1988), 17p (Berry et al 1996), 17q11.1-q12 (Padma et al 1995), 17q24 (Armitage et al 1995), 20p12-q12 (Yamada et al 2000), 21q22.3 (Litt et al 1998), and 22q11.2 (Hulsebos et al 1995).…”