Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights.,Clinical Genetics

当前位置： X-MOL 学术 › Clin. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights.
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-08-02 , DOI: 10.1111/cge.13825
Mohamed S Abdel-Hamid ₁ , Sherif F Abdel-Ghafar ₁ , Suzan R Ismail ₂ , Lubna M Desouky ₂ , Mahmoud Y Issa ₃ , Laila K Effat ₁ , Maha S Zaki ₃

Affiliation

Micro and Martsolf syndromes are rare clinically and genetically overlapping disorders caused by mutations in RAB3GAP1, RAB3GAP2, RAB18 and TBC1D20 genes. We describe 34 new patients, 27 with Micro and seven with Martsolf. Patients presented with the characteristic clinical manifestations of the two syndromes, including postnatal microcephaly, congenital cataracts, microphthalmia, optic atrophy, spasticity and intellectual disability. Brain imaging showed in the majority of cases polymicrogyria, thin corpus callosum, cortical atrophy, and white matter dysmyelination. Unusual additional findings were pectus excavatum (four patients), pectus carinatum (three patients), congenital heart disease (three patients) and bilateral calcification in basal ganglia (one patient). Mutational analysis of RAB3GAP1 and RAB3GAP2 revealed 21 mutations, including 14 novel variants. RAB3GAP1 mutations were identified in 22 patients with Micro, including a deletion of the entire gene in one patient. On the other hand, RAB3GAP2 mutations were identified in two patients with Micro and all Martsolf patients. Moreover, exome sequencing unraveled a TBC1D20 mutation in an additional family with Micro syndrome. Our results expand the phenotypic and mutational spectrum associated with Micro and Martsolf syndromes. Due to the overlapped severities and genetic basis of both syndromes, we suggest to be comprehended as one entity “Micro/Martsolf spectrum” or “RAB18 deficiency.”

中文翻译：

34 名新患者的 Micro 和 Martsolf 综合征：完善表型谱和进一步的分子见解。

Micro 和 Martsolf 综合征是罕见的临床和遗传重叠疾病，由RAB3GAP1、RAB3GAP2、RAB18和TBC1D20基因突变引起。我们描述了 34 名新患者，其中 27 名使用 Micro，7 名使用 Martsolf。患者出现两种综合征的特征性临床表现，包括出生后小头畸形、先天性白内障、小眼症、视神经萎缩、痉挛和智力障碍。在大多数情况下，脑成像显示多小脑回、薄胼胝体、皮质萎缩和白质髓鞘形成障碍。不寻常的额外发现是漏斗胸（四名患者）、鸡胸肉（三名患者）、先天性心脏病（三名患者）和双侧基底节钙化（一名患者）。RAB3GAP1和RAB3GAP2 的突变分析揭示了 21 个突变，包括 14 个新变体。RAB3GAP1在 22 名 Micro 患者中发现了突变，包括一名患者的整个基因缺失。另一方面，在两名 Micro 患者和所有 Martsolf 患者中发现了RAB3GAP2突变。此外，外显子组测序揭示了另一个患有微综合征的家族中的TBC1D20突变。我们的结果扩展了与 Micro 和 Martsolf 综合征相关的表型和突变谱。由于两种综合征的严重程度和遗传基础重叠，我们建议将其理解为一个实体“Micro/Martsolf 谱”或“RAB18 缺乏症”。

更新日期：2020-08-02

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11