Molecular Pathology of Hereditary Neuropathy

遗传性神经病的分子病理学

• 批准号: 11470167
• 负责人: HAYASAKA Kiyoshi
• 金额: $ 8.83万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470167/
• 关键词: 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

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.

对211个遗传性神经病家系进行分析，发现36个家系存在染色体17p11.2的重复，7个家系存在染色体17p11.2的缺失，3个家系存在外周髓鞘蛋白22（PMP 22）基因突变，11个家系存在连接蛋白32基因突变。长春新碱给药后，3例患者出现症状。与国外资料相比，由于染色体17p11.2重复引起的家系较少，且大多数家系的病因不明。她有一个染色体17 p11.2缺失的外周髓鞘蛋白22基因（PMP 22）和一个Arg 157 Gly突变。我们分离了人SCN 8A的cDNA，髓鞘相关糖蛋白（MAG）是一种对周围神经系统具有特异性的电压门控钠通道α亚基，是腓骨肌萎缩症的候选者。由于来源不明，将该基因作为家系的候选基因，然而，在这些家系中未检测到突变。MAG基因可能与病理状态无关。

项目成果

Kato M et al.: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann.Neurology. 47. 514-516 (2000)

Kato M 等人：“前脑无裂畸形患者中的音刺猬信号肽突变。”Ann.Neurology。

Kato M 他: "Sonic hedgehog signal peptide mutaion in a patient with holoprosencephaly."Ann. Neurology. (in press).

Kato M 等人：“前脑无裂畸形患者的声波刺猬信号肽突变”（Ann）。

Numakura C 他: "Hemizygous mutation of the PMP22 gene associated with Charcot-Marie-Tooth Disease Type 1"Ann. Neurology. 47(1). 101-103 (2000)

Numakura C 等人：“与 1 型腓骨肌萎缩症相关的 PMP22 基因的半合子突变”Ann. 47(1) (2000)。

Numakura C et al.: "Hemizygous mutation of the PMP22 gene associated with Charcot-Marie-Tooth Disease Type 1"Ann.Neurology. 47. 101-103 (2000)

Numakura C 等人：“与 1 型腓骨肌萎缩症相关的 PMP22 基因的半合子突变”Ann.Neurology。

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)

Kato M 等人：“日本 X 连锁无脑畸形和双皮质综合征患者中双皮质素基因的新突变”Hum.Genet.. 104. 341-344 (1999)