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首页> 外文期刊>Journal of genetics >Holoprosencephaly: Report of four cases and genotype-phenotype correlations
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Holoprosencephaly: Report of four cases and genotype-phenotype correlations

机译：头颅前脑病：四例报告及基因型与表型的相关性

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Holoprosencephaly (HPE) is a heterogeneous disorder with variable expressivity and reduced penetrance. The causes vary from environmental factors to pure genetic forms, namely chromosomal and genomic abnormalities in up to 70% of the cases, and heterozygous mutations in at least four major genes in 17% of cases (Dubourg et al. 2004; Solomon etal. 2011). Haploinsufficiency of the sonic hedgehog (SHH) (M1M: 600725) gene represents the most frequent cause, either by loss-of-function gene mutations, or by 7q36 genomic deletions. In those latter cases genotype/phenotype correlations are complicated by the contiguous presence of a homeobox gene, HLXB9, located 1.2 Mb telomeric to SHH, involved in the Currarino syndrome, which is characterized by malformations of structures derived from the caudal region of the embryo (Lynch et al. 2000). Moreover, Currarino syndrome exhibits variable expressivity and reduced penetrance. In the present study we report four cases of HPE, three postnatal and one prenatal, displaying different genetic alterations (a novel SHH point mutation and three genomic deletions involving 7q36 chromosomal region) and different clinical features. In the case of SHH point mutation, a 'pure' HPE phenotype was found, whereas a more complex syndrome, with associated vertebral, renal, genital, cardiac abnormalities, was observed in the cases with 7q36 terminal deletion. We describe rare clinical findings, like craniovertebral hinge dysplasia, Hirschsprung's disease and syringomyelia as part of the Currarino syndrome spectrum.
机译：全息前脑（HPE）是一种异质性疾病，具有可变的表达能力和较低的外显率。其原因从环境因素到纯遗传形式不等，即高达70％的病例为染色体和基因组异常，至少17％的病例为至少四个主要基因的杂合突变（Dubourg等，2004; Solomon等，2011）。 ）。声波刺猬（SHH）（M1M：600725）基因的单倍剂量不足是最常见的原因，其原因是功能丧失的基因突变或7q36基因组缺失。在后一种情况下，基因型/表型的相关性由于同位框基因HLXB9（与SHH端粒位于1.2 Mb末端）的连续存在而复杂化，该基因与Currarino综合征有关，其特征是源自胚胎尾部区域的结构畸形（ Lynch等（2000）。此外，库拉里诺综合症表现出可变的表现力和较低的外显率。在本研究中，我们报告了4例HPE，3例产后和1例产前，表现出不同的遗传改变（一种新的SHH点突变和3个涉及7q36染色体区域的基因组缺失）和不同的临床特征。在SHH点突变的情况下，发现“纯” HPE表型，而在7q36末端缺失的病例中观察到更复杂的综合症，伴有椎，肾，生殖器，心脏异常。我们描述了罕见的临床发现，例如颅骨枢纽发育不良，Hirschsprung病和脊髓空洞症，这是Currarino综合征谱的一部分。

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