A novel variant in UBE3A in a family with multigenerational intellectual disability and developmental delay

Molecular Genetics & Genomic Medicine

Xuechao Zhao¹  Li Wang¹  Yuting Zheng¹  Xiangdong Kong¹  Shiyue Mei²  Yanhong Wang² 

[1] Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University Zhengzhou China;Henan Provincial Key Laboratory of Children's Genetics And Metabolic Diseases Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Children's Hospital Zhengzhou China;

关键词: Angelman syndrome;    intellectual disability;    missense variant;    UBE3A gene;   

DOI  :  10.1002/mgg3.1883

来源: DOAJ

【 摘 要 】

Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder and is characterized by severe cognitive disability, motor dysfunction, speech impairment, hyperactivity, and frequent seizures. Although the maternal chromosomal region 15q11.2‐q13 deletion is the most common mechanism of AS, ~10% of individuals with AS are caused by the intragenic variants in the maternally inherited UBE3A, which encodes an E3 ubiquitin ligase. Methods Clinical diagnoses were based on detailed clinical findings. Trio‐based exome sequencing was performed on the proband and her parents to identify the underlying genetic variants. The candidate variants were confirmed by Sanger sequencing following PCR amplification. In silico analyses were conducted to predict the effect of the identified variant on the function of UBE3A protein. Results We identified a novel variant c.2029G>C (p. Gly677Arg) in UBE3A as the most promising candidate. In silico analyses showed that p.Gly677Arg in the UBE3A affects a highly conserved residue. Her mother had the variant at this locus. Sanger sequencing results showed that II‐2, II‐5, II‐7, IV‐1, III‐5, III‐7, III‐8, and III‐9 have the variant c.2029G>C, and all patients inherited maternally variant in UBE3A, while the offsprings of the male carrier were unaffected. Conclusions We identified a novel variant (c.2029G>C) in the UBE3A in a Chinese family with multigenerational intellectual disability and developmental delay. Our findings expanded the genotypic spectrum of AS and provided important information for genetic counseling.

【 授权许可】

Unknown