Exome sequencing identifies KIAA1377 and C5orf42 as susceptibility genes for monomelic amyotrophy

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• 作者：Young-Min Lim^a ; ¹ ; ^{lim_y_m@hanmail.net} ; InSong Koh^b ; ¹ ; Young-Mi Park^c ; ¹ ; Jae-Jung Kim^c ; Dae-Seong Kim^d ; Hyo-Jin Kim^a ; Kyu-Heum Baik^e ; Hye-Yeon Choi^e ; Gap-Seok Yang^e ; Eva Also-Rallo^f ; Eduardo F. Tizzano^f ; Josep Gamez^g ; Kiejung Park^h ; Han-Wook Yooⁱ ; Jong-Keuk Lee^c ; ^{cookie_jklee@hotmail.com} ; Kwang-Kuk Kim^a ; ^{kkkim@amc.seoul.kr}
• 关键词：C5orf42 ; Exome sequencing ; KIAA1377 ; Monomelic amyotrophy
• 刊名：Neuromuscular Disorders
• 出版年：2012
• 期刊代码：203_09608966
• 类别：med
• 出版时间：May, 2012
• 卷：22
• 期：5
• 页码：394-400
• 文件大小：311 K

摘要

Precise topographic localization, predominance in males mostly of Asian origin, and existence of some familial cases suggest a genetic background for monomelic amyotrophy. To identify susceptibility genes for monomelic amyotrophy, we performed whole-exome sequencing of four unrelated patients with monomelic amyotrophy and detected a total of 45 novel nonsynonymous single-nucleotide polymorphisms as unique variants to monomelic amyotrophy compared to control exomes. Genetic association analysis showed significant association with monomelic amyotrophy in the Gly668Ser variant of the KIAA1377 gene (odds ratio = 4.62, P-value = 0.0040) and the Pro1794Leu variant of the C5orf42 gene (odds ratio = 4.63, P-value = 0.0040). Moreover, the combination of two variants increased the risk of monomelic amyotrophy (P = 1.4 脳 10^鈭?, OR = 61.69, 95%confidence interval = 9.62-394.94, in case of combination of two heterozygotes). These data suggest that KIAA1377 and C5orf42 synergistically play a role as susceptibility genes for monomelic amyotrophy.