ESPE Abstracts

Background: Bardet Biedl syndrome(BBS) is a type of non-motile ciliopathy primarily characterized by retinal dystrophy, obesity, polydactyly, cognitive impairment, urogenital anomalies and renal abnormalities. To date, 26 genes have been reported to be associated with BBS: BBS1-BBS21, IFT74, SCLT1, SCAPER and NPHP1. BBS is genetically heterogeneous with significant clinical overlap with other ciliopathies, further complicate the diagnosis of this syndrome. There are a few case reports of BBS patients in China, but no clinical data has been analyzed in detail. Thus, our study aims to describe the genotypic and phenotypic spectra of BBS in China, and elucidate genotype-phenotype correlation.

Methords: 20 Chinese patients diagnosed with BBS were enrolled, the clinical manifestations were documented and exome sequencing were performed. We compared the phenotypes between Chinese BBS patients and those with BBS in Spain, Germany and India to analyze the phenotype differences across patients worldwide. We also summarized all previously reported cases of Chinese BBS patients (94 patients) and identified common and specific variants in the Chinese population. Besides, genotype-phenotype correlation were described in our cohort.

Results: 20 BBS patients from 18 unrelated families were included in this study, aged from 5-34 years old, and 28 BBS variants, of which 15 are novel, in 5 different BBS-associated genes were confirmed. Mutations were predominant in BBS2 (21.28%) and BBS7 (17.02%), and the most commonly variants were BBS2:c.534+1G>T(10 alleles) and BBS7:c.1002delT(7 alleles), which were different from the genotypic spectra of BBS abroad. Comparing BBSome genes(BBS2, 7, 9) versus chaperonin-like genes(BBS10, 12) phenotypes, we found that patients with chaperonin-like genes had an earlier age of onset(p <. 01) and diagnosis(p <. 01), while patients with BBSome genes BMI were higher(p <. 05) and more vision problems(p <. 05).

Conclusion: We recruited 20 Chinese BBS patients for genetic and phenotypic analyses, identified common clinical manifestations, pathogenic genes and variants in Chinese BBS patients. We also described the phenotypic differences across patients worldwide and different BBS-associated genes. This is the largest cohort of Chinese BBS patients, expanding the spectrum of the genotypes and phenotypes associated with this condition.