RESUMEN
Mutations in the GJB1 gene are the second most frequent cause of Charcot-Marie-Tooth disease (CMT), accounting for approximately 10% of CMT cases worldwide. We retrospectively analyzed detailed clinical and neurophysiological data on four Brazilian families carrying novel mutations of the GJB1 gene. Mutations were identified by bidirectional Sanger sequence analysis on the GJB1 coding region. We identified a total of 12 subjects from four different kindred. There was no male-to-male transmission, and their clinical pictures were within the expected spectrum for GJB1-related neuropathy. Males were more severely affected than females. Five out of the eight females only had subclinical neuropathy. Nerve conduction velocities were in the intermediate range in the male patients and higher in the females affected. These mutations increase the genotypic variability associated with GJB1.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Conexinas/genética , Genotipo , Mutación , Adolescente , Adulto , Anciano , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/genética , Linaje , Fenotipo , Estudios Retrospectivos , Adulto Joven , Proteína beta1 de Unión ComunicanteRESUMEN
Compound forms of Charcot-Marie-Tooth (CMT) disease have been recently associated with unusually severe neuropathies, an observation that prompted the proposition that the additive effects of two mutations should be searched in patients whose clinical severity falls outside the common CMT phenotypes. In this report, we present a father and a daughter with a very mild and unusual disease that segregates with two mutations in PMP22 gene, the 17p11.2-p12 duplication and a Ser72Leu point mutation. We propose that the deleterious effects of each mutation are partially compensated by the functional effect of the other.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/diagnóstico , Enfermedad de Charcot-Marie-Tooth/genética , Mutación , Proteínas de la Mielina/genética , Adulto , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Fenotipo , Mutación PuntualRESUMEN
We report an 18-month-old Charcot-Marie-Tooth type 1A (CMT1A) patient who developed a rapid-onset neuropathy, with proximal and distal weakness, and non-uniform nerve conduction studies. The neuropathy responded well to immunomodulation, confirming the coexistence of an inherited and an inflammatory neuropathy. Unexpected clinical and/or electrophysiological manifestations in CMT1A patients should alert clinicians to concomitant inflammatory neuropathy. In addition, this association raises reflections about disease mechanism in CMT1A.