title: Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan.
abstract: Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, has been classified into two types, demyelinating and axonal types. We previously analyzed the genes causing dominant demyelinating CMT in 227 Japanese patients to identify the genetic background, but could not find any mutations in 110 patients. To investigate the frequency of patients with autosomal recessive demyelinating CMT (CMT4) mutations, we analyzed the coding sequence of known causative genes of CMT4 in 103 demyelinating CMT patients, excluding seven patients owing to lack of specimens. We found one patient with a GDAP1 mutation, one patient with an MTMR2 mutation, two patients with SH3TC2/KIAA1985 mutations and three patients with FGD4 mutations. Twelve patients, including five previously detected patients with PRX mutations, were diagnosed as CMT4, accounting for 5.5% of demyelinating CMT. In the patient with GDAP1 mutation, only one mutation inherited from his mother was detected by genomic sequencing. Analysis by reverse transcription polymerase chain reaction using messenger RNA (mRNA) from the patient's leukocytes revealed the absence of transcription from the allele inherited from his father, suggesting the existence of one more mutation leading to a lack or destabilization of mRNA. Most patients carrying CMT4 gene mutations present with early-onset and slowly progressive symptoms, which may be associated with the function of mutants. We could not identify the disease-causing gene in 96 patients (about 45%). Further studies including studies with next-generation sequencers will be required to identify the causative gene in Japanese CMT.
authors: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors: Makiko
authors: M
authors: Hayashi
authors: Akiko
authors: A
authors: Abe
authors: Tatsufumi
authors: T
authors: Murakami
authors: Satoshi
authors: S
authors: Yamao
authors: Hidee
authors: H
authors: Arai
authors: Hideji
authors: H
authors: Hattori
authors: Mizue
authors: M
authors: Iai
authors: Kyoko
authors: K
authors: Watanabe
authors: Nobuyuki
authors: N
authors: Oka
authors: Keiji
authors: K
authors: Chida
authors: Yumiko
authors: Y
authors: Kishikawa
authors: Kiyoshi
authors: K
authors: Hayasaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D055815:Young Adult
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins