CMT gene mutation research - from Japan

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1: Hum Mutat 2002 Nov;20(5):392-8

Molecular analysis in Japanese patients with Charcot-Marie-Tooth

disease: DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations.

Numakura C, Lin C, Ikegami T, Guldberg P, Hayasaka K.

Department of Pediatrics, Yamagata University School of Medicine,

Yamagata, Japan.

Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder and is

traditionally classified into two major types, CMT type 1 (CMT1) and CMT

type 2 (CMT2). Most CMT1 patients are associated with the duplication of

17p11.2-p12 (CMT1A duplication) and small numbers of patients have

mutations of the peripheral myelin protein 22 (PMP22), myelin protein

zero (MPZ), connexin 32 (Cx32/GJB1), and early growth response 2 (EGR2)

genes.

Some mutations of MPZ and Cx32 were also associated with the clinical

CMT2 phenotype. We constructed denaturing gradient gel electrophoresis

(DGGE) analysis as a screening method for PMP22, MPZ, and Cx32 mutations

and studied 161 CMT patients without CMT1A

duplication. We detected 27 mutations of three genes including 15 novel

mutations; six of PMP22, three of MPZ, and six of Cx32. We finally

identified 21 causative mutations in 22 unrelated patients and five

polymorphic mutations.

Eighteen of 22 patients carrying PMP22, MPZ, or Cx32 mutations presented

with CMT1 and four of them with MPZ or Cx32 mutations presented with the

CMT2 phenotype. DGGE analysis was sensitive for screening for those gene

mutations, but causative gene mutation was not identified in many of the

Japanese patients with CMT, especially with CMT1. Other candidate genes

should be studied to elucidate the genetic basis of

Japanese CMT patients. Copyright 2002 Wiley-Liss, Inc.