Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) and genetic heterogeneity

Kouji Maeda, Ryuji Kaji, Katsuhito Yasuno, Jamiyansuren Jambaldorj, Hiroyuki Nodera, Hiroshi Takashima, Masanori Nakagawa, Satoshi Makino, Gen Tamiya

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) is an adult-onset peripheral neurodegenerative disorder which has been reported only in the Okinawa Islands, Japan. The disease locus of "Okinawa- type" HMSN-P has been previously mapped to 3q13.1, with all affected individuals sharing an identical haplotype around the locus, suggesting that the undiscovered causative mutation in HMSN-P originated from a single founder. We have newly found two large families from the western part of Japan within which multiple members developed symptoms similar to those exhibited by HMSN-P patients from Okinawa, with no record of affinal connection between the islands. Using these pedigrees with "Kansai-type" HMSN-P, we carried out a linkage study utilizing eight microsatellite markers and identified a candidate region on 3q13.1 cosegregating with the disease (maximum two-point LOD score of 8.44 at θ = 0.0) overlapping with the Okinawa-type HMSN-P locus. However, the disease haplotype shared among all affected members in these families was different from that in the Okinawa kindred, suggesting allelic heterogeneity. Such allelic variation should aid in the identification of the disease-causative gene. Moreover, the allelic heterogeneity of HMSN-P in the Japanese population suggests that HMSN-P may be more common across other ethnic groups, but classified into other disease categories.

Original languageEnglish
Pages (from-to)907-914
Number of pages8
JournalJournal of Human Genetics
Volume52
Issue number11
DOIs
Publication statusPublished - 2007 Nov
Externally publishedYes

Keywords

  • Amyotrophic lateral sclerosis (ALS)
  • Charcot-Marie-Tooth disease (CMT2P)
  • Hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P)
  • Hereditary motor neuropathy (HMN)
  • Limb-girdle muscular dystrophy (LGMD)
  • Spinal muscular atrophy (SMA)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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