Gonadal mosaicism in severe Pallister-Hall syndrome
Gonadal mosaicism in severe Pallister-Hall syndrome
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DOI：
10.1002/ajmg.a.20338
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发表时间：
2004-01-30
影响因子：
2
通讯作者：
Biesecker, LG
中科院分区：
文献类型：
--
作者：
Ng, D;Johnston, JJ;Biesecker, LG
Pallister-Hall综合征（PHS，MIM#146510）的特征是中央和轴后多指（趾）、下丘脑错构瘤（HH）、双膈会厌、无肛、肾异常和肺分割异常。它是以常染色体显性模式遗传的。在这里，我们描述了一个家庭的两个受影响的儿童表现出严重的PHS与智力迟钝，行为问题，和顽固性癫痫发作。父母都是健康的，与正常的智力，并没有畸形的身体，喉镜检查，头颅MRI examin. The非典型介绍这些孩子和父母的表现的情况下，建议一个常染色体隐性遗传模式或性腺镶嵌。GLI 3基因测序显示，在外显子15（c.3385（-）3386 delTT）两个核苷酸缺失预测移码和提前终止密码子1129（p.F1129X）在儿童，而父母双方都有野生型等位基因。GLI 3基因内标记的基因分型显示，两个孩子都从母亲那里遗传了异常等位基因，因此支持性腺镶嵌作为遗传的潜在机制（证实了亲子关系）。这是第一个报告的情况下，性腺镶嵌在小灵通。这些儿童严重的中枢神经系统表现让人想起非综合征性HH儿童，这些儿童通常患有进行性精神发育迟缓，伴有行为问题和顽固性癫痫发作。我们的结论是，PHS的表型谱可以包括严重的中枢神经系统的表现和复发的风险，PHS应包括一个但书性腺镶嵌，虽然频率不能计算从一个单一的情况下报告。2003年出版Wiley-Liss，Inc（匕首）。
Pallister-Hall syndrome (PHS,MIM#146510) is characterized by central and postaxial polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate anus, renal abnormalities, and pulmonary segmentation anomalies. It is inherited in an autosomal dominant pattern. Here, we describe a family with two affected children manifesting severe PHS with mental retardation, behavioral problems, and intractable seizures. Both parents are healthy, with normal intelligence, and have no malformations on physical, laryngoscopic, and cranial MRI exam. The atypical presentation of these children and the absence of parental manifestations suggested an autosomal recessive mode of inheritance or gonadal mosaicism. Sequencing of GLI3 revealed a two nucleotide deletion in exon 15 (c.3385(-)3386delTT) predicting a frameshift and premature stop at codon 1129 (p.F1129X) in the children while both parents have wild type alleles. Genotyping with GLI3 intragenic markers revealed that both children inherited the abnormal allele from their mother thus supporting gonadal mosaicism as the underlying mechanism of inheritance (paternity was confirmed). This is the first reported case of gonadal mosaicism in PHS. The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures. We conclude that the phenotypic spectrum of PHS can include severe CNS manifestations and that recurrence risks for PHS should include a proviso for gonadal mosaicism, though the frequency cannot be calculated from a single case report. Published 2003 Wiley-Liss, Inc(dagger).