[A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement].
Rinsho Shinkeigaku
; 54(11): 911-5, 2014.
Article
en Ja
| MEDLINE
| ID: mdl-25420567
BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy; symptoms include distal wasting and weakness, usually with some sensory impairment. The clinical course is typically benign and the disease is not life threatening; however, in some cases, severe phenotypes include serious respiratory distress. CASE REPORT: Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). This mutation was considered pathogenic based on molecular evidence; notably, it was unique in that all other reported GARS mutations associated with severe phenotypes are located in an anticodon-binding domain, while in this case in an apparently non-functional region of the GARS gene. Not a simple loss-of-function mechanism, but rather gain-of-function mechanisms have also been reported in GARS mutations. This case provided useful information for understanding the mechanism of CMT2D/dSMA-V.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Músculos Respiratorios
/
Enfermedad de Charcot-Marie-Tooth
/
Músculos Faciales
/
Glicina-ARNt Ligasa
/
Mutación
Límite:
Female
/
Humans
/
Middle aged
Idioma:
Ja
Revista:
Rinsho Shinkeigaku
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Japón