Bardet-Biedl Syndrome
(BBS) is a rare inherited disorder resulting
in multiple organ dysfunctions, whose cardinal clinical features include
cognitive impairment, obesity, and renal dysfunction. Although it
is highly heterogeneous at genetic levels, BBS10 is
one of the major causative genes worldwide. The BBS10 protein is part
of a multiprotein complex localized at the basal body of the primary
cilium. With the advancement of sequencing technologies, novel missense
mutations are regularly reported in BBS10. However,
prioritizing missense variants and conducting further in-depth analysis
are key challenges in addressing their pathogenic effect. This study
aims to characterize the known missense mutations of BBS10 by combining nine different in silico tools (SIFT,
SNAP2, PROVEAN, Align-GVGD, ConSurf, I Mutant, MuPro, PremPS, and
Dynamut) and molecular dynamics (MD) simulations. A total of 101 BBS10 missense variants have been analyzed. Our results
showed that six BBS10 missense variants (Ser191Leu,
Cys19Gly, Ile342Thr, Cys371Ser, Ala417Glu, and Tyr613Cys) were potentially
deleterious. Overall, this study provides a comprehensive workflow
for screening BBS10 missense mutations to identify pathogenic variants
effectively.
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