Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals.
Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals.
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DOI：
10.1136/jmg.2009.073049
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发表时间：
2010-08
影响因子：
4
通讯作者：
Muenke M
中科院分区：
文献类型：
--
作者：
Solomon BD;Lacbawan F;Mercier S;Clegg NJ;Delgado MR;Rosenbaum K;Dubourg C;David V;Olney AH;Wehner LE;Hehr U;Bale S;Paulussen A;Smeets HJ;Hardisty E;Tylki-Szymanska A;Pronicka E;Clemens M;McPherson E;Hennekam RC;Hahn J;Stashinko E;Levey E;Wieczorek D;Roeder E;Schell-Apacik CC;Booth CW;Thomas RL;Kenwrick S;Cummings DA;Bous SM;Keaton A;Balog JZ;Hadley D;Zhou N;Long R;Vélez JI;Pineda-Alvarez DE;Odent S;Roessler E;Muenke M
前脑无裂畸形（HPE）是人类前脑最常见的畸形，可能是由于细胞遗传学异常，致畸剂，发生在综合征的背景下，或由于与非综合征HPE相关的单个基因突变。ZIC2是一种位于染色体13q32上的转录因子，其突变是非综合征性、非染色体HPE的第二常见原因。来自1000多名患有HPE谱系疾病的个体及其亲属的血液样本分析了ZIC 2的序列变异。我们检查了临床细节，并通过文献检索和与其他中心的合作，纳入了所有其他已知的先前发表和未发表的ZIC2突变病例。我们在8%的HPE先证者中发现了ZIC2突变，并描述了来自116个无关激酶的153个个体，包括137名ZIC2分子确定突变的患者和16名ZIC2基因座缺失的患者。与其他基因突变引起的HPE不同，绝大多数病例是散发性的，HPE类型的比例分布与先前发表的非染色体非综合征HPE分析显著不同。此外，我们描述了一种新的面部表型的患者ZIC2突变，其中包括双颞狭窄，上植睑裂，鼻前倾鼻孔短，广泛和界限分明的人中，和大耳朵。这种表型不同于与非染色体、非综合征型HPE相关的标准面部畸形。我们的研究结果表明，由于ZIC2突变引起的HPE与由于其他基因突变引起的HPE不同。这可能有助于阐明面部和前脑形成的机制，并可能有助于指导遗传咨询和诊断策略。
Holoprosencephaly (HPE) is the most common malformation of the human forebrain, and may be due to cytogenetic anomalies, teratogens, occur in the context of a syndrome, or be due to mutations in single genes associated with non-syndromic HPE. Mutations in ZIC2, a transcription factor located on chromosome 13q32, are the second-most common cause of non-syndromic, non-chromosomal HPE. Blood samples from over 1000 individuals with HPE-spectrum disorders and their relatives were analyzed for sequence variations in ZIC2. We examined clinical details and included all other known previously published and unpublished cases of mutations in ZIC2 through a literature search and collaboration with other centers. We find mutations in ZIC2 in 8% of probands with HPE, and describe 153 individuals from 116 unrelated kindreds, including 137 patients with molecularly-determined mutations in ZIC2 and 16 patients with deletions of the ZIC2 locus. Unlike HPE due to mutations in other genes, the vast majority of cases are sporadic and the proportional distribution of HPE types differs significantly from previously published analyses of non-chromosomal non-syndromic HPE. Furthermore, we describe a novel facial phenotype in patients with mutations in ZIC2 which includes bitemporal narrowing, upsplanting palpebral fissures, a short nose with anteverted nares, and a broad and well-demarcated philtrum, and large ears. This phenotype is distinct from the standard facial dysmorphisms associated with non-chromosomal, non-syndromic HPE. Our findings show that HPE due to mutations in ZIC2 is distinct from that due to mutations in other genes. This may shed light on the mechanisms that contribute to the formation of the face and the forebrain and may help direct genetic counseling and diagnostic strategies.
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影响因子：
2
作者：
Orioli, Ieda M.;Castilla, Eduardo E.
通讯作者：
Castilla, Eduardo E.
影响因子：
3.5
作者：
Nanni, L;Ming, JE;Muenke, M
通讯作者：
Muenke, M
影响因子：
3.5
作者：
Brown, LY;Odent, S;Muenke, M
通讯作者：
Muenke, M
DOI：
10.1002/tera.1420160304
发表时间：
1977-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
MATSUNAGA, E;SHIOTA, K
通讯作者：
SHIOTA, K
影响因子：
5.3
作者：
Cheng, Xun;Hsu, Ching-mei;Monuki, Edwin S.
通讯作者：
Monuki, Edwin S.