Luo Shulin, Ren Lingyan, Wang Rongping, Hu Jianxin, Wei Wei, Feng Yurong, Huang Shengwen
Department of Medical Genetics/Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, 550003, China.
Department of Medical Imaging, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, 550003, China.
Heliyon. 2024 May 8;10(10):e30285. doi: 10.1016/j.heliyon.2024.e30285. eCollection 2024 May 30.
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. 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 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 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 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of . Therefore, our findings contributed to the mutation spectrum of the gene and may be useful in the diagnosis and gene therapy of MCPH.
常染色体隐性遗传原发性小头畸形（MCPH，OMIM：251200）是一种神经发育障碍，其特征是脑容量显著减小，尤其是大脑皮层，但脑结构正常且智力残疾无进展。已确定 基因为引发原发性小头畸形的基因（MCPH1，OMIM：607117）。在此，我们报告一例由该基因的新型变异导致的常染色体隐性遗传原发性小头畸形病例。通过磁共振成像（MRI）测量头围，同时使用韦氏智力量表评估受测个体的智力。使用B超评估性腺发育，精液常规检查评估精子状态。对先证者进行全外显子测序（WES）。对先证者的父母进行桑格测序，以确定MCPH1基因中的新型变异是否存在。通过小基因方法验证突变对 剪接的影响。观察到先证者患有常染色体隐性遗传原发性小头畸形和无精子症。鉴定出该基因的一个新型剪接位点纯合突变（c.233+2T＞G），该突变遗传自其父母。小基因方法证实c.233+2T＞G可影响 的剪接。因此，我们的发现丰富了该基因的突变谱，可能有助于MCPH的诊断和基因治疗。
