Novel homozygous protein‐truncating mutation of BBS9 identified in a Chinese consanguineous family with Bardet–Biedl syndrome

Molecular Genetics & Genomic Medicine

Hai‐Yan Tang¹  Fen Xie²  Xiao‐Liu Shi³  Ru‐Chun Dai⁴ 

[1] Center for Medical Genetics School of Life Sciences Central South University Changsha Hunan China;Department of Endocrinology and Metabolism Xiangtan Central Hospital Xiangtan Hunan China;Department of Medical Genetics The Second Xiangya HospitalCentral South University Changsha Hunan China;Department of Metabolism & Endocrinology The Second Xiangya HospitalCentral South University Changsha Hunan China;

关键词: BBS;    BBS9;    NMD;    null mutation;   

DOI  :  10.1002/mgg3.1731

来源: DOAJ

【 摘 要 】

Abstract Background Bardet–Biedl syndrome (BBS) is a rare and genetically heterogeneous disease with a broad spectrum of clinical features, including but not limited to rod‐cone dystrophy, postaxial polydactyly, central obesity, intellectual disability, hypogonadism, and renal dysfunction. Twenty‐one BBS (Bardet–Biedl syndrome) genes have been identified to date. There is minimal mutation information on BBS in Chinese populations and the exact pathogenic mechanism of the null mutation of BBS9 remains unknown. Methods A patient from a Chinese consanguineous family presented with polydactyly, truncal obesity, intellectual disability, genital anomaly, and retinitis pigmentosa was analyzed in this study. Blood DNA and RNA were extracted from the blood of the proband and the parents. The proband was screened for mutations by whole‐exome sequencing. The likely pathogenic mutation detected in the proband was further confirmed by the Sanger sequence in the family. Real‐time RT‐PCR was used to measure the expression of BBS9 in the proband and the control. Results Targeted exome sequencing identified a novel homozygous null mutation (NM_198428.3: c.445C>T) in the 6th exon of the BBS9 gene in the proband and Sanger sequencing was used to validate the heterozygosity in the parents. The mutation was validated to induce the nonsense‐mediated decay of BBS9 messenger RNAs by real‐time RT‐PCR. Conclusions The molecular findings helped to explain the clinical manifestations. The novel homozygous pathogenic variation expanded the mutational spectrum of the BBS9 gene in the Chinese population and will help to understand the pathogenic mechanism of BBS9 null mutation.

【 授权许可】

Unknown