Orioli I M, Castilla E E, Ming J E, Nazer J, Burle de Aguiar M J, Llerena J C, Muenke M
Department of Pediatrics and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Hum Genet. 2001 Jul;109(1):1-6. doi: 10.1007/s004390100537.
Holoprosencephaly (HPE) is genetically heterogeneous with four genes, SIX3, SHH, TGIF, and ZIC2 that have been identified to date and that are altered in 12% of patients. To analyze this prevalence in a South American population-based sample (57 HPE cases in 244,511 live and still births or 1 in 4300), we performed a mutational study of these genes in 30 unrelated children (26 newborns and 4 non-newborns) with HPE being ascertained by ECLAMC (Latin American Collaborative Study of Congenital Malformations). We identified three novel mutations: two were missense mutations of the SHH gene (Cys183-->Phe; His140-->Pro); the third mutation was a 2-bp deletion in the zinc-finger region of the ZIC2 gene. These molecular results explained 8% (2/26 newborn samples) of the HPE cases in this South American population-based sample, a proportion similar to our previously published data from a collection of cases.
全前脑畸形（HPE）具有遗传异质性，迄今已鉴定出四个基因，即SIX3、SHH、TGIF和ZIC2，12%的患者这些基因发生改变。为了分析南美基于人群样本中的这一患病率（244,511例活产和死产中有57例HPE病例，即1/4300），我们对30名无关儿童（26名新生儿和4名非新生儿）的这些基因进行了突变研究，这些儿童的HPE由拉丁美洲先天性畸形协作研究（ECLAMC）确定。我们鉴定出三个新突变：两个是SHH基因的错义突变（Cys183→Phe；His140→Pro）；第三个突变是ZIC2基因锌指区域的2-bp缺失。这些分子结果解释了该南美基于人群样本中8%（2/26个新生儿样本）的HPE病例，这一比例与我们之前发表的病例集数据相似。
