Abstract
BackgroundTo identify the genetic defects and investigate the possible mechanism of cataract genesis in a five-generation family with autosomal dominant congenital posterior polar cataracts.MethodsClinical data were collected, and the lens phenotypes of the affected members in this family were recorded by slit lamp photography. Genomic DNA was isolated from peripheral blood using QIAamp DNA Blood Mini Kits. Twenty-three mutational hot spots associated with autosomal dominant congenital posterior polar cataracts were screened by PCR-based DNA sequencing. Properties and structural models of wild-type and mutant alpha-B (αB)-crystallin (CRYAB) were generated and analyzed using SWISS-MODEL.ResultsAll affected individuals in this family started to exhibit poor vision at the age of 8–10 years. The lens opacity consisted of a single, well-defined plaque, 0.5–3 mm in diameter, which was confined to the posterior pole of the lens. DNA sequencing analysis of the affected members showed a novel, heterozygous missense mutation c.59C > G (P20R) in exon 1 of the CRYAB gene. This mutation was not found in 10 unaffected family members, or in 200 unaffected and unrelated individuals, thereby excluding the possibility that it is a rare polymorphism. Data generated using the ProtScale and PyMOL programs revealed that the mutation altered the stability and solubility of the αB-crystallin protein.ConclusionsThis study reported a novel c.59C > G (P20R) missense mutation in CRYAB in a five-generation Chinese family with posterior polar cataract.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2415-14-108) contains supplementary material, which is available to authorized users.
Highlights
To identify the genetic defects and investigate the possible mechanism of cataract genesis in a five-generation family with autosomal dominant congenital posterior polar cataracts
The water-soluble crystallins are the most abundant proteins in the lens and have a critical role in maintaining lens transparency. They are mainly composed of two related proteins, αA- and αB-crystallins, encoded by the CRYAA and CRYAB genes, which are present in a 3:1 ratio
The CRYAB gene comprises three exons and encodes a small, 175 amino acid protein belonging to the small heat shock protein (sHSP) family [19], which acts as a molecular chaperone, preventing the aggregation of denatured proteins after the exposure to stresses, such as heat shock, radiation, oxidative stress and anticancer drugs [20]
Summary
To identify the genetic defects and investigate the possible mechanism of cataract genesis in a five-generation family with autosomal dominant congenital posterior polar cataracts. The water-soluble crystallins are the most abundant proteins in the lens and have a critical role in maintaining lens transparency They are mainly composed of two related proteins, αA- and αB-crystallins, encoded by the CRYAA and CRYAB genes, which are present in a 3:1 ratio. Both proteins belong to the small heat shock protein (sHSP) family and function as molecular chaperones to prevent the stress-induced aggregation of other proteins [17]. The CRYAB gene comprises three exons and encodes a small, 175 amino acid protein belonging to the sHSP family [19], which acts as a molecular chaperone, preventing the aggregation of denatured proteins after the exposure to stresses, such as heat shock, radiation, oxidative stress and anticancer drugs [20]. Mutations in the CRYAB gene cause distinct clinical phenotypes, including isolated cataract, myofibrillar myopathy, cardiomyopathy, or a multi-systemic disorder combining these features [18]
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