X-linked Alport syndrome : Mutation survey over all 51 exons of the COL4A5 gene

X连锁Alport综合征：COL4A5基因全部51个外显子的突变调查

• 批准号: 07671249
• 负责人: YOSHIKAWA Norishige
• 金额: $ 1.6万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671249/
• 关键词: X-linked Alport syndrome; glomerular basement membrane; type IV collagen alpha5 chain; mutations; COL4A5; RT-PCR; direct sequence; mRNA

Alport syndrome is an inherited disorder characterized by progressive nephritis with ultrastructural basket-weave changes of the glomerular basement membrane (GBM) and neurosensory deafness. The most frequent type, X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the type IV collagen alpha5 chain (alpha5 (IV) ).Mutation analysis of all 51 exons of the COL4A5 gene has been performed by some groups. However, These surveys were performed by SSCP analysis using genomic DNA and the detection rate of mutations was less than 50%. In this study we performed mutation survey over all 51 exons of the COL4A5 gene by reverse transcription-polymerase chain reaction (RT-PCR) and direct sequence using mRNA.Mutations were detected in all male patients and 78% of female patients. Our result help in the design of a better strategy for mutation identification in X-linked Alport syndrome and facilitate genotype-phenotype correlations.

Alport 综合征是一种遗传性疾病，其特征是进行性肾炎，伴有肾小球基底膜 (GBM) 的超微结构篮状编织变化和神经感觉性耳聋。最常见的类型 X 连锁 Alport 综合征是由编码 IV 型胶原 α5 链 (alpha5 (IV) ) 的 COL4A5 基因突变引起的。一些小组已对 COL4A5 基因的所有 51 个外显子进行了突变分析。然而，这些调查是通过基因组DNA的SSCP分析进行的，突变的检出率低于50%。在这项研究中，我们通过逆转录聚合酶链式反应（RT-PCR）和mRNA直接测序对COL4A5基因的所有51个外显子进行了突变调查。在所有男性患者和78%的女性患者中检测到突变。我们的结果有助于设计更好的策略来识别 X 连锁 Alport 综合征的突变，并促进基因型与表型的相关性。

项目成果

Kitagawa K,Nakanishi K,Iijima K,Nishio H,Sano K,Sado Y,Nakamura H,Yoshikawa N.: "Mutation in alpha5 (IV) collagen chain gene in nonfamilial hematuria." J Am soc Nephrol. 6. 264-268 (1995)

Kitakawa K、Nakanishi K、Iijima K、Nishio H、Sano K、Sado Y、Nakamura H、Yoshikawa N.：“非家族性血尿中 α5 (IV) 胶原链基因的突变。”

Nakanishi,K: "Expression of type IV collagen α3 and α4 chain mRDAs in X-linked Alport syndrome" Journal American Society of Naphrology. (In press). (1996)

Nakanishi, K：“X 连锁 Alport 综合征中 IV 型胶原蛋白 α3 和 α4 链 mRDA 的表达”，美国肾脏病学会杂志（1996 年出版）。

吉川 徳茂: "遺伝性糸球体疾患" カレントテラピー. 15. 34-38 (1997)

Norishige Yoshikawa：“遗传性肾小球疾病”《当前疗法》15. 34-38 (1997)。

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吉川纪重：“阿尔波特综合征”医学。 32. 2017-2019（1995）

Nakanishi K,Yoshikawa N,Iijima K,Nakamura H.: "Expression of type IV collagen alpha3 and alpha4 chain mRNAs in X-linked Alport syndrome." J Am soc Nephrol. 7. 938-945 (1996)

Nakanishi K、Yoshikawa N、Iijima K、Nakamura H.：“X 连锁 Alport 综合征中 IV 型胶原 α3 和 α4 链 mRNA 的表达。”