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

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,...

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Autores principales: Dallali, Hamza, Kheriji, Nadia, Kammoun, Wafa, Mrad, Mehdi, Soltani, Manel, Trabelsi, Hajer, Hamdi, Walid, Bahlous, Afef, Ben Ahmed, Melika, Mahjoub, Faten, Jamoussi, Henda, Abdelhak, Sonia, Kefi, Rym
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526562/
https://www.ncbi.nlm.nih.gov/pubmed/34691137
http://dx.doi.org/10.3389/fgene.2021.664963
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author Dallali, Hamza
Kheriji, Nadia
Kammoun, Wafa
Mrad, Mehdi
Soltani, Manel
Trabelsi, Hajer
Hamdi, Walid
Bahlous, Afef
Ben Ahmed, Melika
Mahjoub, Faten
Jamoussi, Henda
Abdelhak, Sonia
Kefi, Rym
author_facet Dallali, Hamza
Kheriji, Nadia
Kammoun, Wafa
Mrad, Mehdi
Soltani, Manel
Trabelsi, Hajer
Hamdi, Walid
Bahlous, Afef
Ben Ahmed, Melika
Mahjoub, Faten
Jamoussi, Henda
Abdelhak, Sonia
Kefi, Rym
author_sort Dallali, Hamza
collection PubMed
description 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.
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spelling pubmed-85265622021-10-21 Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report Dallali, Hamza Kheriji, Nadia Kammoun, Wafa Mrad, Mehdi Soltani, Manel Trabelsi, Hajer Hamdi, Walid Bahlous, Afef Ben Ahmed, Melika Mahjoub, Faten Jamoussi, Henda Abdelhak, Sonia Kefi, Rym Front Genet Genetics 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. Frontiers Media S.A. 2021-10-06 /pmc/articles/PMC8526562/ /pubmed/34691137 http://dx.doi.org/10.3389/fgene.2021.664963 Text en Copyright © 2021 Dallali, Kheriji, Kammoun, Mrad, Soltani, Trabelsi, Hamdi, Bahlous, Ben Ahmed, Mahjoub, Jamoussi, Abdelhak and Kefi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Dallali, Hamza
Kheriji, Nadia
Kammoun, Wafa
Mrad, Mehdi
Soltani, Manel
Trabelsi, Hajer
Hamdi, Walid
Bahlous, Afef
Ben Ahmed, Melika
Mahjoub, Faten
Jamoussi, Henda
Abdelhak, Sonia
Kefi, Rym
Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
title Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
title_full Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
title_fullStr Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
title_full_unstemmed Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
title_short Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
title_sort multiallelic rare variants in bbs genes support an oligogenic ciliopathy in a non-obese juvenile-onset syndromic diabetic patient: a case report
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526562/
https://www.ncbi.nlm.nih.gov/pubmed/34691137
http://dx.doi.org/10.3389/fgene.2021.664963
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