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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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.664963/full |
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| author | Hamza Dallali Nadia Kheriji Wafa Kammoun Mehdi Mrad Manel Soltani Hajer Trabelsi Walid Hamdi Afef Bahlous Melika Ben Ahmed Faten Mahjoub Henda Jamoussi Henda Jamoussi Sonia Abdelhak Sonia Abdelhak Rym Kefi Rym Kefi |
| author_facet | Hamza Dallali Nadia Kheriji Wafa Kammoun Mehdi Mrad Manel Soltani Hajer Trabelsi Walid Hamdi Afef Bahlous Melika Ben Ahmed Faten Mahjoub Henda Jamoussi Henda Jamoussi Sonia Abdelhak Sonia Abdelhak Rym Kefi Rym Kefi |
| author_sort | Hamza Dallali |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T19:07:40Z |
| format | Article |
| id | doaj.art-ad233d3064ed4150bbaef109375d9e5a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-17T19:07:40Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-ad233d3064ed4150bbaef109375d9e5a2022-12-21T21:35:57ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.664963664963Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case ReportHamza Dallali0Nadia Kheriji1Wafa Kammoun2Mehdi Mrad3Manel Soltani4Hajer Trabelsi5Walid Hamdi6Afef Bahlous7Melika Ben Ahmed8Faten Mahjoub9Henda Jamoussi10Henda Jamoussi11Sonia Abdelhak12Sonia Abdelhak13Rym Kefi14Rym Kefi15Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, TunisiaCentral Laboratory of Medical Biology, Institut Pasteur in Tunis, Tunis, TunisiaCentral Laboratory of Medical Biology, Institut Pasteur in Tunis, Tunis, TunisiaCentral Laboratory of Medical Biology, Institut Pasteur in Tunis, Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur in Tunis, Tunis, TunisiaCentral Laboratory of Medical Biology, Institut Pasteur in Tunis, Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur in Tunis, Tunis, TunisiaResearch Unit on Obesity, National Institute of Nutrition and Food Technology, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, TunisiaResearch Unit on Obesity, National Institute of Nutrition and Food Technology, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, TunisiaUniversity of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur in Tunis, Tunis, TunisiaUniversity of Tunis El Manar, Tunis, TunisiaJuvenile-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.https://www.frontiersin.org/articles/10.3389/fgene.2021.664963/fullmonogenic diabeteswhole exome sequencingBardet-Biedl syndromeoligogenic inheritancebioinformatic analysiscase report |
| spellingShingle | Hamza Dallali Nadia Kheriji Wafa Kammoun Mehdi Mrad Manel Soltani Hajer Trabelsi Walid Hamdi Afef Bahlous Melika Ben Ahmed Faten Mahjoub Henda Jamoussi Henda Jamoussi Sonia Abdelhak Sonia Abdelhak Rym Kefi Rym Kefi 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 monogenic diabetes whole exome sequencing Bardet-Biedl syndrome oligogenic inheritance bioinformatic analysis 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 | monogenic diabetes whole exome sequencing Bardet-Biedl syndrome oligogenic inheritance bioinformatic analysis case report |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.664963/full |
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