Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report

Frontiers in Genetics

Afef Bahlous¹  Mehdi Mrad¹  Hajer Trabelsi¹  Manel Soltani¹  Nadia Kheriji²  Hamza Dallali²  Wafa Kammoun²  Walid Hamdi³  Melika Ben Ahmed³  Faten Mahjoub⁴  Henda Jamoussi⁴  Sonia Abdelhak⁵  Rym Kefi⁵ 

[1] Central Laboratory of Medical Biology, Institut Pasteur in Tunis, Tunis, Tunisia;Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, Tunisia;Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur in Tunis, Tunis, Tunisia;Research Unit on Obesity, National Institute of Nutrition and Food Technology, Tunis, Tunisia;University of Tunis El Manar, Tunis, Tunisia;

关键词: monogenic diabetes;    whole exome sequencing;    Bardet-Biedl syndrome;    oligogenic inheritance;    bioinformatic analysis;    case report;   

DOI  :  10.3389/fgene.2021.664963

来源: DOAJ

【 摘 要 】

Juvenile-onset diabetes may occur in the context of a rare syndromic presentation, suggesting a monogenic etiology rather than a common multifactorial diabetes. In the present study, we report the case of a young diabetic Tunisian patient presenting learning problems, speech deficits, short stature, brachydactyly, and a normal weight. Whole exome sequencing analysis revealed five heterozygous genetic variants in BBS1, BBS4, BBS8, MKS1, and CEP290. These genes are involved in the regulation of cilium biogenesis and function. We analyzed variant combinations pathogenicity using the recently developed ORVAL tool, and we hypothesized that cumulative synergetic effects of these variants could explain the syndromic phenotype observed in our patient. Therefore, our investigation suggested a genetic diagnosis of Bardet–Biedl syndrome with an oligogenic inheritance pattern rather than a monogenic diabetes. Although there is no curative therapy for this ciliopathy at the moment, a genetic diagnosis may offer other supportive care options, including the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension, as well as the genetic counseling for family members.

【 授权许可】

Unknown