AUTHOR=Yan Kai , Sun Yixi , Yang Yanmei , Liu Bei , Dong Minyue 

TITLE=Case Report: Identification Pathogenic Abnormal Splicing of BBS1 Causing Bardet–Biedl Syndrome Type I (BBS1) due to Missense Mutation

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.849562

DOI=10.3389/fgene.2022.849562

ISSN=1664-8021

ABSTRACT=Conventionally, protein features affected by missense mutation were attribute to destroy important domain with amino acid alternation and it was difficult to clearly specify the pathogenicity of a novel missense mutation. Nevertheless, the associations between missense mutations and abnormal splicing are nowadays increasingly reported. Rarely, some missense mutations, locating at the non-canonical splicing sites, are observed to damage the splicing process. In this study, a couple has three adverse pregnancy history that the affected fetus presented typical polydactyly, renal abnormalities and cerebral ventriculomegaly. To identify its genetic etiology, whole-exome sequencing was performed and the missense mutation c.1339G>A was identified, which was located at the non-canonical splicing sites of the BBS1 gene. Then, reverse transcription polymerase chain reaction was carried out and demonstrated extra 115bp originating from Intron 13 cut into cDNA which generated a predicted premature termination codon (PTC) in the BBS1 protein. Further expression analysis by using Real-time reverse-transcribed PCR confirmed the occurrence of nonsense-mediated decay (NMD). Therefore, the pathogenicity of the missense mutation c.1339G>A was explicit and our study helped to extend the spectrum of pathogenic mutations in Bardet-Biedl syndrome type I.