AUTHOR=Zhang Li , Teng Yanling , Hu Haoran , Zhu Huimin , Wen Juan , Liang Desheng , Li Zhuo , Wu Lingqian 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1052915

DOI=10.3389/fgene.2022.1052915

ISSN=1664-8021

ABSTRACT=Background: Seckel syndrome (SCKL) is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restriction, 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 suspected Chinese SCKL family with 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, quantitative real-time polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) were conducted to confirm the pathogenicity of novel variants, respectively.
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 spectrums 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.