PDF(Pubmed)
Abstract：
Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1，OMIM: 607117). Here we report a case of autosomal recessive primary microcephaly as caused by a novel variant in the MCPH1 gene. Head circumference was measured by Magnetic Resonance Imaging (MRI), while the Wechsler Intelligence Scale was used to evaluate the intelligence of the individual being tested. B-ultrasound was used to assess gonadal development, and semen routine was used to assess sperm status. The whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was conducted on the parents of the proband to determine if the novel variant in the MCPH1 gene was present. The effect of the mutation on the splicing of MCPH1 was verified by minigene approach. It was observed that the proband had autosomal recessive primary microcephaly and azoospermatism. A novel splice-site homozygous mutation (c.233+2T > G) of the MCPH1 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of MCPH1. Therefore, our findings contributed to the mutation spectrum of the MCPH1 gene and may be useful in the diagnosis and gene therapy of MCPH.
摘要：
常染色体复发性原发性显微镜（MCPH，OMIM：251200）是一种神经发育障碍，其特征是大脑大小明显减少，特别是在大脑皮层，但具有正常的大脑结构和非进行性智力障碍。MCPH1已被鉴定为引发原发性小头畸形的基因（MCPH1，OMIM：607117）。在这里，我们报告了一例由MCPH1基因的新变体引起的常染色体隐性遗传原发性小头畸形。通过磁共振成像（MRI）测量头围，而韦氏智力量表用于评估被测试个体的智力。B超用于评估性腺发育，精液常规用于评估精子状态。对先证者进行全外显子组测序(WES)。对先证者的亲本进行Sanger测序以确定MCPH1基因中是否存在新变体。通过小基因方法验证了突变对MCPH1剪接的影响。观察到先证者有常染色体隐性原发性小头畸形和无精子症。鉴定了MCPH1基因的一个新的剪接位点纯合突变（c.233+2T>G），从他父母那里继承的.Minigene方法证实c.233+2T>G可以影响MCPH1的剪接。因此,我们的发现有助于MCPH1基因的突变谱,可能对MCPH的诊断和基因治疗有帮助.
