Exome sequencing identifies KIAA1377 and C5orf42 as susceptibility genes for monomelic amyotrophy
Por:
Lim, YM, Koh, I, Park, YM, Kim, JJ, Kim, DS, Kim, HJ, Baik, KH, Choi, HY, Yang, GS, Also-Rallo, E, Tizzano, EF, Gamez, J, Park, K, Yoo, HW, Lee, JK, Kim, KK
Publicada:
1 may 2012
Resumen:
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 x 10(-5), 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. (C) 2011 Elsevier B.V. All rights reserved.
Filiaciones:
Lim, YM:
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul 138736, South Korea
Koh, I:
Hanyang Univ, Coll Med, Dept Physiol, Seoul 133791, South Korea
Park, YM:
Univ Ulsan, Coll Med, Asan Inst Life Sci, Seoul 138736, South Korea
Kim, JJ:
Univ Ulsan, Coll Med, Asan Inst Life Sci, Seoul 138736, South Korea
Kim, DS:
Pusan Natl Univ, Yangsan Hosp, Dept Neurol, Res Inst Convergence Biomed Sci & Technol, Pusan 609735, South Korea
Kim, HJ:
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul 138736, South Korea
Baik, KH:
Macrogen Inc, Seoul, South Korea
Choi, HY:
Macrogen Inc, Seoul, South Korea
Yang, GS:
Macrogen Inc, Seoul, South Korea
Also-Rallo, E:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
CIBERER U705, Barcelona, Spain
Tizzano, EF:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
CIBERER U705, Barcelona, Spain
Gamez, J:
Hosp Vall de Hebron, Dept Neurol, Barcelona, Spain
Park, K:
Natl Inst Hlth, Ctr Genome Sci, Chungwon, South Korea
Yoo, HW:
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pediat, Seoul 138736, South Korea
Lee, JK:
Univ Ulsan, Coll Med, Asan Inst Life Sci, Seoul 138736, South Korea
Kim, KK:
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul 138736, South Korea
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