Bardet-Biedl syndrome in a Chinese patient with a novel homozygous BBS5 variant from paternal uniparental disomy.

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive genetic disorder with multi-systemic symptoms, including polydactyly, obesity, renal anomalies, retinal dystrophy, and cognitive impairment. Our study reported a previously unreported BBS5 homozygous variant in a Chinese patient with BBS from paternal uniparental disomy. A comprehensive ophthalmologic examination was conducted. Whole-exome sequencing and Sanger sequencing were utilized to detect pathogenic variants. Protein structure prediction and multiple sequence alignment were performed. An 18-year-old female presented with blurry vision and night blindness since childhood. Upon conducting a general assessment, polydactyly, obesity and learning disability were also identified. Ophthalmologic examination revealed severe retinal degeneration. Whole-exome and Sanger sequencing detected a homozygous BBS5 variant (NM_152384.3: exon 3: c.185del; p.L62Wfs*16), with the homozygosity from paternal uniparental disomy. The protein structure prediction showed substantial deletions of amino acid segments caused by the variant. Multiple sequence alignment indicated that the amino acids corresponding to the variant were in a highly conserved region of the BBS5 protein, underscoring their essential role in maintaining protein function. Our study identified a novel homozygous BBS5 variant from paternal uniparental disomy. These findings expand the genotypic and phenotypic spectrum of Bardet-Biedl syndrome.