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CMA analysis identifies homozygous deletion of MCPH1 in 2 brothers with primary Microcephaly-1

机译：CMA分析识别2兄弟的纯合缺失Microcephaly-1

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Homozygous mutations and deletions of the microcephalin gene (MCPH1; OMIM *607117) have been identified as a cause of autosomal recessive primary microcephaly and intellectual disability (MIM #251200). Previous studies in families of Asian descent suggest that the severity of the phenotype may vary based on the extent of the genomic alteration. We report chromosome microarray (CMA) findings and the first described family study of a patient with primary microcephaly in a consanguineous Hispanic family. The proband, a boy born at full-term to consanguineous parents from Mexico, presented at 35?months of age with microcephaly, abnormal brain MRI findings, underdeveloped right lung, almond-shaped eyes, epicanthal folds, bilateral esotropia, low hairline, large ears, smooth philtrum, thin upper lip, and developmental delay. MRI of the brain showed a small dermoid or lipoma (without mass effect) within the interpeduncular cistern and prominent arachnoid granulation. The underdeveloped right lung was managed with long-acting inhaled corticosteroids. Otherwise the proband did not have any other significant medical history. The proband had 2 older brothers, ages 14 and 16, from the same consanguineous parents. The 14-year-old brother had a phenotype similar to that of the proband, while both parents and the oldest brother did not have the same phenotypic findings as the proband. The SNP-based CMA analysis of the proband detected a homozygous 250-kb microdeletion at 8p23.2p23.1, extending from 6,061,169 to 6,310,738?bp [hg19]. This genomic alteration encompasses the first 8 exons of MCPH1. Follow-up studies detected the same homozygous deletion in the affected brother, segregating with microcephaly and intellectual disability. Regions of homozygosity (ROHs) were also observed in the affected brother. Since ROHs are associated with an increased risk for recessive disorders, presence of ROH may also contribute to the phenotype of the affected brothers. The parents were both hemizygous for the deletion. Here we report a homozygous deletion of multiple exons of the MCPH1 gene that was associated with primary microcephaly and intellectual disability in a Hispanic family. In the context of previous studies, our results support the idea that deletions involving multiple exons cause a more severe phenotype than point mutations.
机译：已经鉴定了微骨蛋白基因的纯合突变和缺失的微骨基因（MCPH1; OMIM * 607117）作为常染色体隐性原发性微微术和智力残疾的原因（MIM＃251200）。以前的亚洲血统家族的研究表明，表型的严重程度可能根据基因组改变的程度而变化。我们报告染色体微阵列（CMA）调查结果，以及患有近亲西班牙裔家庭中患有原发性微微症的患者的第一次描述的家庭研究。该副本，一个由墨西哥的近期父母出生的一个男孩，在35岁时呈现出微头，脑脑MRI调查结果异常，右肺，杏仁形眼睛，涩根折叠，双侧北方症，大发际线，大耳朵，光滑的菲尔特，薄的上唇和发育延迟。大脑的MRI显示出在通风腔内腔室内的小浸泡或脂肪瘤（没有质量效应）和突出的蛛网膜造粒。欠发达的右肺进行管理，用长效吸入皮质类固醇进行管理。否则证据没有任何其他重要的病史。概念来自同一个近亲父母，有2岁哥哥，年龄14和16岁。这位14岁的兄弟有一个类似于证据的表型，而父母和最古老的兄弟则没有与证书相同的表型发现。基于SNP的CMA分析证书检测到8p23.2p23.1的纯合250-kb微筛选，从6,061,169到6,310,738〜6,310,738〜6,310,738℃。该基因组改变包括MCPH1的前8个外显子。随访研究发现受影响的兄弟在受影响的兄弟中相同的纯合缺失，用微微透畸形和智力残疾隔离。在受影响的兄弟中也观察到纯合子（RoHS）的区域。由于RoHs与隐性疾病的风险增加有关，因此RoH的存在也可能有助于受影响兄弟的表型。父母都是缺失的嗜血。在这里，我们报告了与西班牙裔家庭中的原发性微微术和智力残疾相关的MCPH1基因的多个外显子的纯合缺失。在先前研究的背景下，我们的结果支持涉及多种外显子的缺失引起比点突变更严重的表型。

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