Wang Ziwei, Li Chuang, Zhao Yan, Li Ling, Lyu Yuan, Cui Hong
Department of Gynecology and Obstetrics, Shengjing Hospital Affiliated to China Medical University, Key Laboratory of Maternal Fetal Medicine of Liaoning Province, Shenyang, Liaoning 110004, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Oct 10;38(10):985-988. doi: 10.3760/cma.j.cn511374-20200714-00514.
To analyze the clinical phenotype and pathogenic variant in a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH).
Clinical phenotype of the child was reviewed. Whole exome sequencing was carried out for the child. Candidate variant was verified by Sanger sequencing of the family member.
The proband manifested dyskinesia, development delay, cerebellar hypoplasia and bilateral hearing impairment. WES results revealed that the proband has carried a pathogenic c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene, which was verified by Sanger sequencing to be a de novo variant.
The c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene probably underlay the MICPCH in the proband. Above finding has provided a basis for genetic counseling. WES should be considered for the diagnosis of neurological dysplasia.
分析一名被诊断为智力发育迟缓、小头畸形伴脑桥和小脑发育不全（MICPCH）儿童的临床表型和致病变异。
回顾该儿童的临床表型。对该儿童进行全外显子组测序。通过对家庭成员进行桑格测序验证候选变异。
先证者表现为运动障碍、发育迟缓、小脑发育不全和双侧听力障碍。全外显子组测序结果显示，先证者携带CASK基因的致病c.1641_1644delACAA（p.Thr548Trpfs*69）变异，经桑格测序验证为新发变异。
CASK基因的c.1641_1644delACAA（p.Thr548Trpfs*69）变异可能是先证者MICPCH的病因。上述发现为遗传咨询提供了依据。对于神经发育异常的诊断应考虑全外显子组测序。
