Abstract
BACKGROUND: The Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder, characterized by clinical and genetic heterogeneity. BBS is more commonly reported in adults and children than in fetuses. Here, a retrospective study on 210 fetuses with congenital renal malformation was conducted. METHODS: The fetuses were diagnosed using invasive prenatal tests, including chromosome karyotype analysis, whole exome sequencing (WES), and single-nucleotide polymorphism array. We found the intrauterine phenotype of a fetus presenting enlarged kidneys, enhanced echo, and oligohydramnios; therefore, the fetus was characterized to have BBS. RESULTS: Chromosome karyotype analysis presented normal results. Analysis using an Affymetrix CytoScan 750K array revealed 2 homozygous regions. However, WES revealed a homozygous mutation of c.1177C>T (p.Arg393*) on exon 12 of BBS1 and a heterozygous variation of c.2704G>A (p.Asp902Asn) on exon 22 of CC2D2A. The American College of Medical Genetics and Genomics guidelines identified c.1177C>T and c.2704G>A as a pathogenic mutation and of uncertain significance, respectively. Sanger sequencing identified heterozygous mutation, that is, c.1177C>T and heterozygous variation, that is, c.2704G>A in the parents of the fetus. CONCLUSIONS: WES identified a novel homozygous nonsense mutation c.1177C>T in BBS1 of a Chinese fetus with congenital renal malformation. This finding provides insight into the BBS1 mutations in Asian populations in general and shows the necessity of genetic counseling.