Two novel variants in CEP152 caused Seckel syndrome 5 in a Chinese family

Frontiers in Genetics

Genetics

Juan Wen¹  Haoran Hu¹  Huimin Zhu¹  Zhuo Li¹  Yanling Teng¹  Li Zhang¹  Lingqian Wu²  Desheng Liang² 

[1]Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, Hunan, China

[2]Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, Hunan, China

[3]Hunan Jiahui Genetics Hospital, Changsha, Hunan, China

关键词: Seckel syndrome;    microcephaly;    CEP152;    whole-exome sequencing;    mRNA splicing;   

DOI  :  10.3389/fgene.2022.1052915

 received in 2022-09-24, accepted in 2022-11-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Seckel syndrome (SCKL) is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restrictions, microcephaly, intellectual disability, and a typical “bird-head” facial appearance. Here, we aimed to identify the genetic etiology of a family with suspected SCKL.Methods: This study enrolled a Chinese family suspected of SCKL with their detailed family history and clinical data. We performed karyotype analysis, copy number variation sequencing (CNV-seq), and trio whole-exome sequencing (WES) to explore the genetic etiology in the proband. Furthermore, the quantitative real-time polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) were conducted to confirm the pathogenicity of novel variants.Results: The karyotype analysis and CNV-seq were normal in the proband. Two novel variants in CEP152, c.1060C>T (p.Arg354*) and c.1414-14A>G, were identified in the proband through trio-WES. The qPCR results showed that the total CEP152 mRNA expression levels were significantly reduced in c.1060C>T (p.Arg354*) and c.1414-14A>G compared with healthy control individuals. Moreover, aberrant skipping of exon 12 due to the non-canonical splice-site variant was revealed by RT-PCR and Sanger sequencing.Conclusion: Our findings expanded pathogenic variant spectra in SCKL and offered new insights into the pathogenicity of a non-classical splice-site variant in CEP152, which provided additional information for helping the family improve pregnancy plans in the future.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Teng, Hu, Zhu, Wen, Liang, Li and Wu.