Basel-Vanagaite L, Pasmanik-Chor M, Lurie R, Yeheskel A, Kjaer K W
Departments of Medical Genetics, Tel-Aviv University, Tel Aviv, Israel.
Mol Syndromol. 2010;1(5):223-230. doi: 10.1159/000327156. Epub 2011 Apr 7.
Hypotrichosis with juvenile macular dystrophy (HJMD) and ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM) are both caused by mutations in the CDH3 gene. In this report, we describe a family with EEM syndrome caused by a novel CDH3 gene mutation and review the mutation spectrum and limb abnormalities in both EEM and HJMD. A protein structure model showing the localization of different mutations causing both syndromes is presented. The CDH3 gene was sequenced and investigation of the mutations performed using a protein structure model. The conservation score was calculated by ConSurf. We identified a novel CDH3 gene mutation, p.G277V, which resides in a conserved residue located on a β-strand in the second cadherin domain. Review of the data on previously published mutations showed intra-familial and inter-familial variations in the severity of the limb abnormalities. Syndactyly was the most consistent clinical finding present in all the patients regardless of mutation type. The results of our study point to a phenotypic continuum between HJMD and EEM. It is important for genetic counseling to keep in mind the possible clinical/phenotypic overlap between these 2 syndromes and to be aware of the possible risk of limb abnormalities in future pregnancies in families with HJMD syndrome. CDH3 gene mutation screening is recommended in patients with both these syndromes as part of the work-up in order to offer appropriate genetic counseling.
毛发稀少伴青少年黄斑营养不良（HJMD）和外胚层发育不良、缺指（趾）畸形与黄斑营养不良（EEM）均由CDH3基因突变引起。在本报告中，我们描述了一个由新型CDH3基因突变导致的EEM综合征家系，并回顾了EEM和HJMD的突变谱及肢体异常情况。展示了导致这两种综合征的不同突变定位的蛋白质结构模型。对CDH3基因进行测序，并使用蛋白质结构模型对突变进行研究。通过ConSurf计算保守性得分。我们鉴定出一种新型CDH3基因突变，p.G277V，该突变位于第二个钙黏蛋白结构域β链上的一个保守残基处。对先前发表的突变数据的回顾显示，肢体异常严重程度存在家族内和家族间差异。并指（趾）畸形是所有患者中最一致的临床发现，与突变类型无关。我们的研究结果表明HJMD和EEM之间存在表型连续性。遗传咨询时牢记这两种综合征可能存在的临床/表型重叠，并意识到HJMD综合征家庭未来妊娠中肢体异常的可能风险非常重要。对于患有这两种综合征的患者，建议进行CDH3基因突变筛查，作为检查的一部分，以便提供适当的遗传咨询。
