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

Abstract

Congenital cataract is a common major abnormality of the eye, which can result in significant visual impairment or blindness in childhood. In this work, we studied four generations of a Chinese family that exhibited autosomal dominant coralliform cataract but no other ocular or systemic abnormalities. Members of the family were firstly genotyped with microsatellite markers at loci associated with congenital cataract on the reported regions of chromosomes 1, 2, 3, 10, 11, 12, 13, 15, 16, 17, 20, 21, and 22, but negative LOD scores were obtained. Following exclusion of these loci, a genome-wide scan was performed, and significant evidence of linkage was obtained for marker D2S2211 (Z = 2.69, h = 0.00). In multipoint analysis, a maximum LOD score 4.87 (h = 0.00) was reached between markers D2S2211 and D2S2164. Haplotype data indicated a coralliform cataract disease gene in a 26-cM interval at a novel disease locus 2p24-pter between D2S297 and D2S2268. No genes related to cataract in this region have been reported so far.

Combinational analysis of linkage and exome sequencing identifies the causative mutation in a Chinese family with congenital cataract

“…Because numerous mutations were detected, we combined whole exome sequencing and linkage analysis to sift through the potential causative mutations. As described previously by Gao et al [11], five loci with positive but non-significant LOD scores (>1) were identified by linkage analysis (Additional file 1: Table S2).…”

“…A total of 19 family members, including 9 affected and 10 unaffected individuals, were recruited for a previous study by Gao et al in 2005 [11]. Three additional individuals (affected III:11, unaffected III:5 and III:8) were newly recruited for this study (Figure 1).…”

“…In a previous study, we presented evidence to suggest some candidate linkage regions in a four-generation Chinese family with autosomal dominant coralliform cataract, but the causal mutation was not identified [11]. In the current study, we have further investigated the same pedigree using whole exome sequencing and linkage combinational analysis to identify the causal mutation.…”

A new locus in chromosome 2q37-qter is associated with posterior polar cataract

“…In order to explore the molecular mechanisms of congenital cataracts and to develop effective approaches to the prevention and therapy of the disease, it is of importance to locate the region of the disease gene and clone candidate genes. Currently, more than 40 loci of autosomal dominant congenital cataracts have been mapped on 13 human chromosomes, which consist of 1p36, 1q21-25, 2q33-36, 2p12, 3q21-22, 10q24-25, 11q22.3-23.1, 12q13, 13cen-q13, 14q22-23, 15q21-22, 16q22.1, 17p13, 17q11-12, 17q24, 20p12-q12, q22.3, and 22q11.2 [3,4]. More than 20 candidate genes have been identified in these loci, and their coding proteins can be classified into four groups: crystallines, membrane transport proteins, cytoskeleton proteins, and transcriptional factors to development-related proteins [3,5].…”

CHMP4B, a Novel Gene for Autosomal Dominant Cataracts Linked to Chromosome 20q

“…2 The majority of associated mutations have been identified in 10 [3][4][5][6][7][8][9][10][11] which encode the major "refractive" proteins of the lens. The remaining mutations have been identified in seven functionally diverse genes, including those coding for gap-junction connexin proteins (GJA3 [MIM 121015], GJA8 [MIM 600897]), 12,13 a heat-shock transcription factor (HSF4 [MIM 602438]), 14 an aquaporin water channel (MIP [MIM 154050]) 15 17,18 In addition to the known genes, at least 10 novel genes for autosomal dominant or recessive forms of nonsyndromic cataracts remain to be identified at loci on chromosomes 1 [19][20][21][22][23][24][25][26][27][28][29][30][31][32] Here we have fine-mapped a locus for autosomal dominant cataracts on chromosome 20q and, subsequently, have identified underlying missense mutations in the gene for chromatin modifying protein-4B (CHMP4B [MIM 610897]), also known as charged multivesicular body protein-4B, which has not previously been associated with human disease.…”