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Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome
Background: Alport syndrome is a hereditary disorder caused by pathogenic variants in the COL4A gene, which can be inherited in an autosomal recessive, dominant, or X-linked pattern. In the Bukharian Jewish population, no founder pathogenic variant has been reported in COL4A4. Methods: The cohort in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606019/ https://www.ncbi.nlm.nih.gov/pubmed/37895203 http://dx.doi.org/10.3390/genes14101854 |
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author | Levy, Michal Bazak, Lily Lev-El, Noa Greenberg, Rotem Kropach, Nesia Basel-Salmon, Lina Maya, Idit |
author_facet | Levy, Michal Bazak, Lily Lev-El, Noa Greenberg, Rotem Kropach, Nesia Basel-Salmon, Lina Maya, Idit |
author_sort | Levy, Michal |
collection | PubMed |
description | Background: Alport syndrome is a hereditary disorder caused by pathogenic variants in the COL4A gene, which can be inherited in an autosomal recessive, dominant, or X-linked pattern. In the Bukharian Jewish population, no founder pathogenic variant has been reported in COL4A4. Methods: The cohort included 38 patients from 22 Bukharian Jewish families with suspected Alport syndrome who were referred the nephrogenetics clinic between 2012 and 2022. The study collected demographic, clinical, and genetic data from electronic medical records, which were used to evaluate the molecular basis of the disease using Sanger sequencing, and next-generation sequencing. Results: Molecular diagnosis was confirmed in 20/38 patients, with each patient having at least one of the three disease-causing COL4A4 variants detected: c.338G<A (p.Gly113Asp), c.3022G>A (p.Gly1008Arg), and c.871-6T>C. In addition, two patients were obligate carriers. Overall, there were 17 heterozygotes, 2 compound heterozygotes, and 3 homozygotes. Each variant was detected in more than one unrelated family. All patients had hematuria with/without proteinuria at referral, and the youngest patient with proteinuria (age 5 years) was homozygous for the c.338G>A variant. End-stage renal disease was diagnosed in two patients at the age of 38 years, a compound heterozygote for c.338G>A and c.871-6T>C. Hearing deterioration was detected in three patients, the youngest aged 40 years, all of whom were heterozygous for c.338G>A. Conclusion: This study unveils three novel disease-causing variants, c.3022G>A, c.871-6T>C, and c.338G>A, in the COL4A4 gene that are recurrent among Jews of Bukharian ancestry, and cause Alport syndrome in both dominant and recessive autosomal inheritance patterns. |
format | Online Article Text |
id | pubmed-10606019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106060192023-10-28 Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome Levy, Michal Bazak, Lily Lev-El, Noa Greenberg, Rotem Kropach, Nesia Basel-Salmon, Lina Maya, Idit Genes (Basel) Article Background: Alport syndrome is a hereditary disorder caused by pathogenic variants in the COL4A gene, which can be inherited in an autosomal recessive, dominant, or X-linked pattern. In the Bukharian Jewish population, no founder pathogenic variant has been reported in COL4A4. Methods: The cohort included 38 patients from 22 Bukharian Jewish families with suspected Alport syndrome who were referred the nephrogenetics clinic between 2012 and 2022. The study collected demographic, clinical, and genetic data from electronic medical records, which were used to evaluate the molecular basis of the disease using Sanger sequencing, and next-generation sequencing. Results: Molecular diagnosis was confirmed in 20/38 patients, with each patient having at least one of the three disease-causing COL4A4 variants detected: c.338G<A (p.Gly113Asp), c.3022G>A (p.Gly1008Arg), and c.871-6T>C. In addition, two patients were obligate carriers. Overall, there were 17 heterozygotes, 2 compound heterozygotes, and 3 homozygotes. Each variant was detected in more than one unrelated family. All patients had hematuria with/without proteinuria at referral, and the youngest patient with proteinuria (age 5 years) was homozygous for the c.338G>A variant. End-stage renal disease was diagnosed in two patients at the age of 38 years, a compound heterozygote for c.338G>A and c.871-6T>C. Hearing deterioration was detected in three patients, the youngest aged 40 years, all of whom were heterozygous for c.338G>A. Conclusion: This study unveils three novel disease-causing variants, c.3022G>A, c.871-6T>C, and c.338G>A, in the COL4A4 gene that are recurrent among Jews of Bukharian ancestry, and cause Alport syndrome in both dominant and recessive autosomal inheritance patterns. MDPI 2023-09-23 /pmc/articles/PMC10606019/ /pubmed/37895203 http://dx.doi.org/10.3390/genes14101854 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Levy, Michal Bazak, Lily Lev-El, Noa Greenberg, Rotem Kropach, Nesia Basel-Salmon, Lina Maya, Idit Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome |
title | Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome |
title_full | Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome |
title_fullStr | Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome |
title_full_unstemmed | Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome |
title_short | Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome |
title_sort | potential founder variants in col4a4 identified in bukharian jews linked to autosomal dominant and autosomal recessive alport syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606019/ https://www.ncbi.nlm.nih.gov/pubmed/37895203 http://dx.doi.org/10.3390/genes14101854 |
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