Arauz R F, Solomon B D, Pineda-Alvarez D E, Gropman A L, Parsons J A, Roessler E, Muenke M
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., USA.
Mol Syndromol. 2010;1(2):59-66. doi: 10.1159/000302285. Epub 2010 Apr 22.
Holoprosencephaly (HPE), the most common malformation of the human forebrain, may arise due to interacting genetic and environmental factors. To date, at least 12 contributory genes have been identified. Fibroblast growth factor 8 (Fgf8) belongs to the FGF family of genes expressed in several developmental signaling centers, including the anterior neural ridge, which is implicated in midline anomalies in mice. In humans, FGF8 mutations have been previously reported in facial clefting and in hypogonadotropic hypogonadism, but have not been reported in patients with HPE. We screened 360 probands with HPE for sequence variations in FGF8 using High Resolution DNA Melting (HRM) and sequenced all identified variations. Here we describe a total of 8 sequence variations in HPE patients, including a putative loss-of-function mutation in 3 members of a family with variable forms of classic HPE, and relate these findings to the phenotypes seen in other conditions.
前脑无裂畸形（HPE）是人类前脑最常见的畸形，可能由遗传和环境因素相互作用引起。迄今为止，已鉴定出至少12个致病基因。成纤维细胞生长因子8（Fgf8）属于FGF基因家族，在几个发育信号中心表达，包括前神经嵴，该区域与小鼠中线异常有关。在人类中，先前已报道FGF8突变与面部裂畸形和低促性腺激素性性腺功能减退有关，但尚未在HPE患者中报道。我们使用高分辨率DNA熔解（HRM）技术对360例HPE先证者进行FGF8序列变异筛查，并对所有鉴定出的变异进行测序。在此，我们描述了HPE患者中总共8种序列变异，包括一个经典HPE不同形式家族中3名成员的一个推定功能丧失突变，并将这些发现与其他疾病中观察到的表型相关联。
