BACKGROUND: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. OBJECTIVE: To report the identification of a mutation in the human CRYGS gene. SUBJECTS AND METHODS: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out. RESULTS: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011). CONCLUSIONS: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.
BACKGROUND: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. OBJECTIVE: To report the identification of a mutation in the humanCRYGS gene. SUBJECTS AND METHODS: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out. RESULTS: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011). CONCLUSIONS: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.
Authors: William D Brubaker; J Alfredo Freites; Kory J Golchert; Rebecca A Shapiro; Vasilios Morikis; Douglas J Tobias; Rachel W Martin Journal: Biophys J Date: 2011-01-19 Impact factor: 4.033
Authors: Jin Jiang; Chongfei Jin; Wei Wang; Xiajing Tang; Xingchao Shentu; Renyi Wu; Yao Wang; Kun Xia; Ke Yao Journal: Mol Vis Date: 2009-01-12 Impact factor: 2.367