Genetic analysis of patients with spinal muscular atrophy

脊髓性肌萎缩症患者的基因分析

• 批准号: 11670744
• 负责人: SAKAKIHARA Youichi
• 金额: $ 2.37万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670744/
• 关键词: spinal muscular atrophy; SMN1; SMN2; SMN遺伝子; マイクロサテライトマーカー

Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative disorder with progressive weakness and atrophy of voluntary muscles. The survival motor neuron gene (SMN) is present in two highly homologues copies (SMN 1 and SMN 2) on chromosome 5q13. Homozygous deletion of exons 7 and 8 of SMN 1 is responsible for SMA. In SMA patients, SMN 2 partially compensate the lack of SMN 1. Previously we reported the relative high incidence of large deletion including SMN1 region in Japanese SMA type I patients. The purpose of this study to demonstrate another genetic back ground of Japanese SMA type I patients investigating the the SMN 1 to SMN 2 ratio in carriers. As expected, in normal individuals there is one copy of each gene on a chromosome (SMN1/SMN2 was 1). In this study we determined the SMN1/SMN2 ratios of 14 parents and one carrier sibling of Japanese type I SMA patients with homozygous deletion of exons 7 and 8 of SMN1. We found that the SMN1/SMN2 ratio was 0.5 or 1 in eleven (73.3%) carriers. Residual four carriers had the SMN1/SMN2 ratio of 1/3. This finding supports the idea that the deletion rather than conversion is the main genetic event in type I SMA. For further insight into the characteristic genetic background of SMA in Japan, identification of gene copy number is essential.

脊髓性肌萎缩症（SMA）是一种常见的常染色体隐性神经退行性疾病，伴有随意肌进行性无力和萎缩。运动神经元存活基因 (SMN) 以两个高度同源的副本（SMN 1 和 SMN 2）存在于染色体 5q13 上。 SMN 1 外显子 7 和 8 的纯合缺失导致 SMA。在 SMA 患者中，SMN 2 部分补偿了 SMN 1 的缺失。之前我们报道过日本 SMA I 型患者中包括 SMN1 区域在内的大缺失发生率相对较高。本研究的目的是展示日本 SMA I 型患者的另一种遗传背景，调查携带者中 SMN 1 与 SMN 2 的比率。正如预期的那样，在正常个体中，染色体上每个基因都有一个拷贝（SMN1/SMN2 为 1）。在本研究中，我们确定了 SMN1 外显子 7 和 8 纯合缺失的日本 I 型 SMA 患者的 14 名父母和一名携带者兄弟姐妹的 SMN1/SMN2 比率。我们发现，11 名携带者 (73.3%) 的 SMN1/SMN2 比率为 0.5 或 1。剩余的四个运营商的SMN1/SMN2比率为1/3。这一发现支持这样的观点，即缺失而不是转换是 I 型 SMA 的主要遗传事件。为了进一步了解日本 SMA 的特征遗传背景，基因拷贝数的鉴定至关重要。

项目成果

Sakakihara Y: "Medicalcare and support for children with mental retardation in school"No to Hattatsu [Brain & Development]. 32(3). 237-241 (2000)

榊原 Y：“对在校智障儿童的医疗和支持”向 Hattatsu 说不 [Brain]

Piep Tran T, Kroepfl. T., Saito M, Sakakihara Y, et al.: "The gene copy ratios of SMN1/SMN2 in Japanese carriers with type I Spinal muscnlar atrephy"Brain & Development. 23(5). 321-326 (2001)

Piep Tran T，Kroepfl。

Tran TD, Kubota M, Sakakihara Y. et al.: "Varicella-associated acte necrotizing enchephalopaty with a good prognosis"Brain & Developneut. 23(1). 54-57 (2001)

Tran TD、Kubota M、Sakakihara Y. 等人：“水痘相关的坏死性脑病具有良好的预后”大脑

Sasaki J, Ishikawa K, Sakakihara Y, Toda T et al.: "Neuronal expression of the fukutin gene"Human Molecular Genetics. 9(20). 3083-3090 (2000)

Sasaki J、Ishikawa K、Sakakihara Y、Toda T 等：“fukutin 基因的神经元表达”人类分子遗传学。