A novel CRYAB mutation resulting in multisystemic disease.
Neuromuscul Disord
; 22(1): 66-72, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21920752
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mutación Puntual
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Predisposición Genética a la Enfermedad
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Cadena B de alfa-Cristalina
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Enfermedades Musculares
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neuromuscul Disord
Asunto de la revista:
NEUROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido