Molecular Pathology of Hereditary Neuropathy

• Project/Area Number: 11470167
• Research Category: Grant-in-Aid for Scientific Research (B).
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yamagata University
• Principal Investigator: HAYASAKA Kiyoshi School of Medicine, Yamagata University Professor, 医学部, 教授 (20142961)
• Co-Investigator(Kenkyū-buntansha): KIMURA Toshiyuki University Hospital, Yamagata University Assistant Professor, 医学部・附属病院, 助手 (90292432) ; KATO Mitsuhiro University Hospital, Yamagata University Lecturer, 医学部・附属病院, 講師 (10292434) ; MITSUI Tetsuo University Hospital, Yamagata University Lecturer, 医学部・附属病院, 講師 (30270846)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥13,800,000 (Direct Cost: ¥13,800,000); Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 1999: ¥10,600,000 (Direct Cost: ¥10,600,000)
• Keywords: hereditary neuropathies / Charcot-Marie-Tooth disease / myelin / peripheral myelin protein 22 / Po / connexin 32 / myelin associated glycoprotein / sodium channel / SCN8A / 膜電位依存性Naチャンネルαサブユニット / Po蛋白

Research Abstract

We analyzed 211 pedigrees with hereditary neuropathies and found 36 pedigrees with a duplication of chromosome 17p 11.2, 7 pedigrees with a deletion of chromosome 17p 11.2, 3 pedigrees with peripheral myelin protein 22 gene (PMP22) gene mutation, and 11 pedigrees with connexin 32 gene mutation. Three patients became symptomatic by vincristine administration. Compared with the data from foreign countries, the pedigrees due to a duplication of chromosome 17p 11.2 were few and most pedigrees were not identified their etiologies.
We studied a female patient who presented with autosomal recessive or sporadic Charcot- Marie-Tooth disease type 1 (CMT1). She had a deletion of chromosome 17p 11.2 containing the peripheral myelin protein 22 gene (PMP22) and an Arg 157 Gly mutation of PMP22.
We isolated the cDNA of human SCN8A, which is a voltage-gated sodium channel α subunits specific for peripheral nervous system as a candidate for Charcot-Marie-Tooth disease.
We analyzed the myelin associated glycoprotein (MAG) gene as a candidate for the pedigrees due to unknown origin, however, the mutation was not detected in those pedigrees. MAG gene seems not be associated with pathological states.

Research Products

• [Publications] Kato M et al.: "A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and double cortex syndrome"Hum.Genet.. 104. 341-344 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shizuka M et al.: "A novel mutation of the myelin Po gene segregating Charcot-Marie-Tooth disease type 1B manifesting trigeminal nerve thickening"J Neurol Neurosurg Psych. 67. 250-251 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato M et al.: "Diffuse pachygyria with cerebellar hypoplasia : a milder form of microlissencephaly or a new genetic syndrome?"Ann.Neurology. 46. 660-663 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Lin C et al.: "Deletion and nonsense mutations of the connexin 32 gene associated with Charcot-Marie-Tooth disease"Tohoku J.exp.Med.. 188. 239-244 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Numakura C et al.: "Hemizygous mutation of the PMP22 gene associated with Charcot-Marie-Tooth Disease Type 1"Ann.Neurology. 47. 101-103 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato M et al.: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann.Neurology. 47. 514-516 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 早坂清: "Annual Review 神経"中外医学社. 324 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato M et al.: "A novel mutaion of the doublecortin gene in Japanese patients with X-linked lissencephaly and double cortex syndrome"Hum.Genet.. 104. 341-344 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shizuka M et al.: "A novel mutation of the myelin Po gene segregating Charcot-Marie-Tooth disease type 1B manifesting trigeminal nerve thickening"J Neurol Neurosurg Psych. 67. 250-251 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato M et al.: "Diffuse pachygyria with cerebellar hypoplasia : a milder form of microlissencephaly or a new genetic syndrome ?"Ann.Neurology. 46. 660-663 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Lin C et al.: "Deletion and nonsense mutations of the connexin 32 gene associated with Charcot-Marie-Tooth disease"Tohoku J.exp.Med.. 188. 239-244 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Numakura C et al.: "Hemizygous mutation of the PMP22 gene associated with Charcot-Marie-Tooth Disease Type 1"Ann.Neurology. 47. 101-103 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato M et al.: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann.Neurology. 47. 514-516 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato M et al.: "A novel mutation of the doublecortin gene in Japanese patients with X -linked lissencephaly and double cortex syndrome"Hum.Genet.. 104. 341-344 (1999)
• [Publications] Shizuka M et al.: "A novel mutation of the myelin Po gene segregating Charcot-Marie-Tooth disease type 1B manifesting trigeminal nerve thickening"J Neurol Neurosurg Psych . 67. 250-251 (1999)
• [Publications] Kato M et al.: "Diffuse pachygyria with cerebellar hypoplasia : a milder form of microlissencephaly or a new genetic syndrome?"Ann. Neurology . 46. 660-663 (1999)
• [Publications] Lin C et al.: "Deletion and nonsense mutations of the connexin 32 gene associated with Charcot-Marie-Tooth disease"Tohoku J.exp.Med.. 188. 239-244 (1999)
• [Publications] Numakura C et al.: "Hemizygous mutation of the PMP22 gene associated with Charcot-Marie-Tooth Disease Type 1"Ann.Neurology. 47. 101-103 (2000)
• [Publications] Kato M et al.: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann.Neurology. 47. 514-516 (2000)
• [Publications] 早坂清: "Annual Review 神経"中外医学社. 324 (2001)
• [Publications] Kato K 他: "A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and double cortex syndrome"Hum. Genet. 104(4). 341-344 (1999)
• [Publications] Shizuka M 他: "A novel mutation of the myelin Po gene segregating Charcot-Marie-Tooth disease type 1B manifesting trigeminal nerve thickening"J. Neurol. Neurosurg. Psych.. 67(2). 250-251 (1999)
• [Publications] Kato M 他: "Diffuse pachygyria with cerebellar hypoplasia: a milder form of microlissencephaly or a new genetic syndrome?"Ann. Neurology. 46(4). 660-663 (1999)
• [Publications] Lin C 他: "Deletion and nonsense mutations of the connexin 32 gene associated with Charcot-Marie-Tooth disease"Tohoku J. exp. Med.. 188(3). 239-244 (1999)
• [Publications] Numakura C 他: "Hemizygous mutation of the PMP22 gene associated with Charcot-Marie-Tooth Disease Type 1"Ann. Neurology. 47(1). 101-103 (2000)
• [Publications] Kato M 他: "Sonic hedgehog signal peptide mutaion in a patient with holoprosencephaly."Ann. Neurology. (in press).