A novel 3-base pair deletion of the CRYAA gene identified in a large Chinese pedigree featuring autosomal dominant congenital perinuclear cataract

Abstract

ABSTRACT. Congenital cataract is caused by reduced transparency of the lens resulting from metabolic disorders during the fetal period. The disease shows great heterogeneity both clinically and genetically. We identified a 4-generation ethnic Han Chinese family affected by autosomal dominant congenital perinuclear cataract. The patients underwent full clinical and ophthalmologic examinations to rule out any concomitant disorders. Blood samples were collected and genomic Novel CRYAA mutation underlying congenital cataract DNA was extracted. Potential mutations in the candidate gene alpha A crystallin (CRYAA) were screened. Prenatal diagnosis was then provided for a fetus of the affected proband by chorionic villus sampling. In all patients, DNA sequencing of the CRYAA gene revealed a novel 3-bp deletion mutation in exon 3 (c.246_248delCGC), which led to deletion of codon 117 encoding arginine (p.117delR) in the peptide chain. The same mutation was not found among unaffected and healthy individuals. Bioinformatic analysis revealed that although the c.246_248delCGC is an 'in-frame' mutation, removal of arginine resulted in a significant change in the protein structure. The fetus did not possess this mutation and was confirmed to be healthy at 1-year follow-up. A novel diseasecausing mutation, c.246_248delCGC (p.117delR), of the CRYAA gene has been identified in a Chinese family with autosomal-type perinuclear congenital cataracts. This is also the first report of prenatal diagnosis of this type of congenital cataract.

Two novel mutations identified in ADCC families impair crystallin protein distribution and induce apoptosis in human lens epithelial cells

“…Crystallins are the predominant lens structural proteins of mammals and have a significant function in providing transparency and light transmission to the eye lens 32 . However, mutations in the genes encoding crystallin proteins lead to abnormal expression, which might disrupt lens opacity and even cause blindness 12 , 33 , 34 .…”

Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract

“…[13,20–22] For example, c.246_248delCGC (p.117delR), a novel mutation of the CRYAA gene, has been detected in a Chinese family with perinuclear congenital cataracts of autosomal type. [15] Su et al [23] also identified a disease-causing mutation in the CRYAA gene, c.161G > C (p.R54P), with autosomal dominant Y-suture cataracts. Jiaox et al [4] have reported 2 novel missense mutations, namely p.R11C and p. R12C of the CRYAB gene, show relations with autosomal recessive congenital nuclear cataracts.…”

“…[14] The CRYAA gene is mapped to chromosome 21q22.3, which consists of 3 exons. [15] Located on chromosome 11q23, CRYAB encodes for a member of the sHSP family composing of 175 amino acid protein, [4] and functions as a molecular chaperone, restraining the accumulation of denatured proteins after exposure to stresses, including radiation, heat shock, and oxidative stress. [13] Currently, over 40 loci have been mapped in congenital cataract development.…”

Label‐free molecular probe based on G‐quadruplex and strand displacement for sensitive and selective detection and naked eye discrimination of exon 2 deletion of AIMP2

“…Cancer is one severe consequence of mutants in the genetic information. Besides widely researched single nucleotide polymorphism, genetic deletion also associated with several diseases, such as a 3‐base pair deletion of CRYAA gene lead to an autosomal dominant congenital perinuclear cataract in large Chinese pedigree . In addition to several bases deletion, exons deletion is also common in genetic mutants.…”