Asunto(s)
Atrofia/genética , Proteínas de Homeodominio/genética , Degeneración Macular/genética , Enfermedades del Nervio Óptico/genética , Transactivadores/genética , Adolescente , Atrofia/patología , Diferenciación Celular/genética , Niño , Preescolar , Femenino , Homocigoto , Humanos , Degeneración Macular/patología , Masculino , Mutación , Enfermedades del Nervio Óptico/patología , Células Ganglionares de la Retina/patologíaRESUMEN
Hereditary deafness is a genetically heterogeneous phenotype for which more than 100 genomic loci have been identified thus far. By analysis of a consanguineous Palestinian family, GPSM2 was recently discovered to be the cause of autosomal recessive non-syndromic hearing loss DFNB82. Here, we report a second truncating mutation, GPSM2 p.Q562X, identified via autozygosity mapping in a consanguineous Turkish family. This report provides evidence for allelic heterogeneity of GPSM2 and confirms its causative role for non-syndromic deafness.
Asunto(s)
Pérdida Auditiva/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Consanguinidad , Femenino , Genes Recesivos , Genotipo , Homocigoto , Humanos , Masculino , Polimorfismo de Nucleótido Simple , TurquíaRESUMEN
Inherited desmosomal cardiocutaneous syndromes are characterized by the quartet of woolly hair, palmoplantar keratoderma (PPK), skin fragility and cardiac abnormalities, which are caused by mutations in genes coding for desmosomal proteins. We describe a previously unrecognized autosomal recessive syndrome in a family with arrhythmogenic right ventricular cardiomyopathy associated with alopecia and PPK (named CAPK). Genetic investigation of the family led us to find a homozygous disease-causing mutation, p.R265H, in JUP which encodes plakoglobin, a well-described member of the desmosome complex. This study expands the clinical spectrum of disorders associated with germline mutations affecting desmosomal proteins by describing a novel phenotype.