A novel CRYAB mutation resulting in multisystemic disease

作者：Sacconi Sabrina^*; Feasson Leonard; Antoine Jean Christophe; Pecheux Christophe; Bernard Rafaelle; Cobo Ana Maria; Casarin Alberto; Salviati Leonardo; Desnuelle Claude; Urtizberea Andoni

来源：Neuromuscular Disorders, 2012, 22(1): 66-72.

DOI：10.1016/j.nmd.2011.07.004

• Myofibrillar myopathy
• Multisystemic involvement
• Alpha-B-crystallin
• CRYAB

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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2012-1