Multiple genetic mutations implicate spectrum of phenotypes in Bardet-Biedl syndrome

• Published in: Gene Vol. 725; p. 144164
• Main Authors: Chakrabarty, Sanjiban, Savantre, Swheta B., Ramachandra Bhat, C., Satyamoorthy, Kapaettu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-01-2020
• Subjects: Bardet-Biedl Syndrome - genetics; Bardet-Biedl Syndrome - metabolism; Bardet–Biedl syndrome; BBS; Chaperonins - genetics; Chaperonins - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 6 - genetics; DNA Mutational Analysis; Genetic Association Studies; High-Throughput Nucleotide Sequencing; Humans; Hypogonadism; Male; Mutation - genetics; PDE6B; Pedigree; Phenotype; Receptors, Androgen - genetics; Retinitis pigmentosa; Retinitis Pigmentosa - genetics; Whole Exome Sequencing - methods; Young Adult; RFT; AR; BBS; Retinitis pigmentosa; PDE6B; FLP; Hypogonadism; BMI; Bardet–Biedl syndrome
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2019.144164

•BBS10, AR and PDE6B mutation identified in two siblings from an Indian family.•First report to show multiple gene mutation in BBS phenotype.•Our study will enhance the knowledge in BBS diagnosis and therapeutics.
Bardet–Biedl syndrome (BBS) is a clinically and genetically heterogeneous ciliopathy with several clinical features including retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioral dysfunction and hypogonadism with wide spectrum of additional features. With multiple phenotypes and heterogeneous distribution, it is unlikely that BBS is caused by single gene defect. We have performed clinical and genetic diagnosis of two individuals from an Indian family with classical BBS symptoms. Whole exome sequencing identified homozygous missense mutation in BBS10 gene, hemizygous missense AR and homozygous missense PDE6B mutations in the proband and affected sibling with BBS. Identification of BBS10 mutation along with AR and PDE6B gene mutation will expand the genetic and phenotypic spectrum in individuals with BBS.