A novel nonsense mutation in BBS4 gene identified in a Chinese family with Bardet-Biedl syndrome

Abstract

BackgroundBardet-Biedl syndrome (BBS) is a genetically heterogeneous disease, and information about BBS in Chinese populations is very limited. The purpose of the present study was to determine the genetic cause of BBS in a Chinese Han family.MethodsClinical data were recorded for the 4-year-old female proband and the available family members. The proband was screened for mutation by Sanger sequencing for a total of 142 exons of the 12 BBS-causing genes (BBS1-BBS12). The variants detected in the proband were further confirmed in the other family members.ResultsWe identified a novel homozygous nonsense mutation (c.70A>T, p.K24X) in theBBS4gene exon 2 in the proband. Such mutant allele was predicted to cause a premature truncation in the N-terminal of the BBS4 protein, and probably induced the nonsense-mediated decay ofBBS4messenger RNAs. The proband's parents and brother were heterozygous for the nonsense mutant allele. It was absent in 50 Chinese control subjects. An additional rare heterozygous missense single nucleotide polymorphism (SNP) named rs200718870 inBBS10gene was also detected in the proband, her father and her brother. Some manifestations of the proband including atypical retinitis pigmentosa, choroidal sclerosis, high myopia, and early onset of obesity might be associated with this mutation inBBS4gene. The proband's father also reported surgical removal of an extra finger during childhood.ConclusionsThe present study described a novel nonsense mutation inBBS4gene in a Chinese family. This homozygous mutation was predicted to completely abolish the synthesis of the BBS4 protein. We also detected a rare heterozygous missense SNP inBBS10gene in the family, but did not find sufficient evidence to support the triallelic inheritance.