Clinical characterization and genetic analysis of a possible novel type of dominant Charcot-Marie-Tooth disease

Lee, Yi-Chung; Lee, Tso-Ching; Lin, Kon-Ping; Lin, Ming-Wei; Chang, Ming-Hong; Soong, Bing-Wen

doi:10.1016/j.nmd.2010.05.001

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Volume 20, Issue 8 , Pages 534-539, August 2010

Clinical characterization and genetic analysis of a possible novel type of dominant Charcot-Marie-Tooth disease

Yi-Chung Lee
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan
Tso-Ching Lee
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
Kon-Ping Lin
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan
Ming-Wei Lin
- Institute of Pubic Health, National Yang-Ming University School of Medicine, Taipei, Taiwan
Ming-Hong Chang
- Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Section of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan
Bing-Wen Soong
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Corresponding author. Address: Department of Neurology, National Yang-Ming University, #155, Sec.2, Li-nung St., Peitou District, Taipei, Taiwan 112, Republic of China. Tel./fax: +886 2 28727577.

Received 10 March 2010; received in revised form 24 April 2010; accepted 5 May 2010.

Abstract

A family of dominant Charcot-Marie-Tooth disease with eleven members, six of them symptomatic, was characterized clinically and genetically. The ages at onset ranged from 10 to 45years, and the clinical severity varied from no symptom to being wheelchair-bound. The median motor nerve conduction velocities ranged from 16.5 to 45.7m/s. Men were more severely affected. The sural nerve biopsies in two patients featured demyelinating changes. No mutation in PMP22, MPZ, GJB1, NEFL, LITAF, EGR2, MFN2, HSP27, HSP22, GADP1, YARS, and DNM2 genes was found in the proband. Haplotype analyzes excluded linkage to the previously reported dominant CMT loci. A genomewide screen with 400 microsatellite markers and multipoint linkage analyzes revealed that the highest LOD score was around 1.6 on chromosome 3q28-q29, suggestive of a weak but possible linkage at this locus. The results of this study implicate the existence of a novel genetic locus for this syndrome.