A novel CRYAB mutation resulting in multisystemic disease
| Autor: | Alberto Casarin, Sabrina Sacconi, Ana Maria Cobo, Leonardo Salviati, Rafaëlle Bernard, Claude Desnuelle, Christophe Pécheux, Jean Christophe Antoine, Andoni Urtizberea, Léonard Féasson |
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| Rok vydání: | 2012 |
| Předmět: |
Male
DNA Mutational Analysis Mutant Mutation Missense Cardiomyopathy Biology Cataract Pathogenesis Muscular Diseases Crystallin Genotype medicine Humans Point Mutation Genetic Predisposition to Disease Genetic Association Studies Genetics (clinical) Aged Genetics alpha-Crystallin B Chain Middle Aged medicine.disease Phenotype Neurology Chaperone (protein) Pediatrics Perinatology and Child Health biology.protein Female Neurology (clinical) Age of onset Cardiomyopathies Molecular Chaperones |
| Zdroj: | Neuromuscular Disorders. 22:66-72 |
| ISSN: | 0960-8966 |
| Popis: | Mutations in the CRYAB gene, encoding alpha-B crystallin, cause distinct clinical phenotypes including isolated posterior polar cataract, myofibrillar myopathy, cardiomyopathy, or a multisystemic disorder combining all these features. Genotype/phenotype correlations are still unclear. To date, multisystemic involvement has been reported only in kindred harboring the R120G substitution. We report a novel CRYAB mutation, D109H, associated with posterior polar cataract, myofibrillar myopathy and cardiomyopathy in a two-generation family with five affected individuals. Age of onset, clinical presentation, and muscle abnormalities were very similar to those described in the R120G family. Alpha-B crystallin may form dimers and acts as a chaperone for a number of proteins. It has been suggested that the phenotypic diversity could be related to the various interactions between target proteins of individual mutant residues. Molecular modeling indicates that residues D109 and R120 interact with each other during dimerization of alpha-B crystallin; interestingly, the two substitutions affecting these residues (D109H and R120G) are associated with the same clinical phenotype, thus suggesting a similar pathogenic mechanism. We propose that impairment of alpha-B crystallin dimerization may also be relevant to the pathogenesis of these disorders. |
| Databáze: | OpenAIRE |
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