【摘要】 目的 探讨钙/钙调蛋白依赖性丝氨酸蛋白激酶（CASK）基因变异导致的巨脑回畸形的临床特征及遗传学特点。方法 回顾1例经Sanger测序确诊的智力障碍伴小头畸形、脑桥发育不良（MICPCH）患儿的临床资料，查阅和学习相关文献，总结同一基因型患者的临床特点。结果 家系3人外显子组测序发现患儿有新发的CASK基因半合子无义突变c.1837C>T/p.R613~*，为既往报道的致病性变异，因此诊断为MICPCH(OMIM#300749)。结论 本例报道提示CASK c.1837C>T在中国人群中可能是1个热点变异，其导致较严重的MICPCH。该变异在公共单核苷酸多态性（SNP）数据库中均无记录，在本地20万人（含10万+患者）外显子组数据库中共检出3例，且均为患者，其中2例为男性。以往报道的MICPCH多见于女性，因此男性新发突变导致的MICPCH应格外引起重视。更多还原

【Abstract】 Objective To investigate the clinical and genetic characteristics of calcium/calmodulin-dependent serine protein kinase(CASK) gene variant. Methods By reviewing the clinical data of a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia(MICPCH) through Sanger sequencing, reviewing and studying relevant literature, and summarizing the clinical characteristics of patients with the same genotype. Results Exome sequencing of three individuals identified the child with a de novo hemizygous nonsense mutation in CASK gene c.1837C>T/p.R613~*, a reported pathogenic variant, which was diagnosed with MICPCH(OMIM#300749). Conclusion This case report suggests that CASK c.1837C>T may be a hotspot mutation in the Chinese population, which leads to more severe MICPCH. This mutation was not recorded in the public single nucleotide polymorphism(SNP) database, but a total of 3 cases were detected in the exome database of 200000 local people(including more than 100000 patients), and all were patients, 2 of whom were male. MICPCH reported in the past is more common in women, so MICPCH caused by new mutations in men should be paid special attention.更多还原