Mutational analysis of SHH and GLI3 in anorectal malformations

作者：Maria‐Mercè Garcia‐Barceló, Vincent Chi‐Hang Lui, Xiaoping Miao, Man‐Ting So, Thomas Yuk-Yu Leon, Zhenwei Yuan, Long Li, Lei Liu, Bin Wang, Xiaobing Sun, Liuming Huang, Jinfa Tou, Esw Ngan, Stacey S. Cherny, KW Chan, Kim‐hung Lee, Weiling Wang, Kenneth Kak‐Yuen Wong, Paul Kwong-Hang Tam · 发表于：Birth Defects Research Part A Clinical and Molecular Teratology · 年份：2008 · DOI：10.1002/bdra.20482 · 被引用次数：19 · 研究领域：Hedgehog Signaling Pathway Studies、Congenital gastrointestinal and neural anomalies、Congenital Ear and Nasal Anomalies

BACKGROUND: Anorectal malformations (congenital absence of the anal opening) are among the most common pediatric surgical problems and carry a significant chronic morbidity. METHODS: Direct sequencing was used to screen 88 anorectal malformations patients for mutations and polymorphisms in SHH and GLI3. These genes were chosen according to the phenotype presented by mutant mice and their expression patterns. RESULTS: We report on 10 GLI3 variants (IVS3+141C>G, T183A, IVS4+124T>C, IVS7+17G>A, IVS8+1 G>C, N503N, P941P, P998L, A1005A, A1039A) and four SHH mutation/variants (IVS1-49C>T, IVS2+111A>C, L214L, G290D). CONCLUSIONS: These variants are not over-represented in the healthy population and most are predicted to be benign. This study conveys the problematic assessment of the pathogenic role in disease of rare point mutations and variants.