Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2

Author(s)

Genari, Adriana Borges ^[1] ; Stefani Borghetti, Vinicius Horacio ^[1] ; Gouvea, Silmara Paula ^[1] ; Bueno, Keity Cristina ^[1] ; dos Santos, Patricia Leila ^[1] ; dos Santos, Antonio Carlos ^[2] ; Barreira, Amilton Antunes ^[1] ; Lourenco, Charles Marques ^[1] ; Marques, Jr., Wilson ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Neurosci & Behav Sci, Sch Med Ribeirao Preto, BR-14040900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Internal Med, Sch Med Ribeirao Preto, Div Radiol, BR-14040900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Neuromuscular Disorders; v. 21, n. 6, p. 428-432, JUN 2011.
• Web of Science Citations: 15

Abstract

Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot Marie Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de nova mutation was found in exon 4 (c.310C > T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes. (C) 2011 Elsevier B.V. All rights reserved. (AU)