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Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies

Autosomal recessive non‐syndromic hearing loss (ARNSHL) is the most common inherited sensory impairment. It is particularly frequent in North African populations who have a high rate of consanguineous marriage. The c.242G>A homozygous variant in LRTOMT gene was previously established as pathogeni...

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Autores principales: Mosrati, Mohamed Ali, Fadhlaoui‐Zid, Karima, Benammar‐Elgaaied, Amel, Gibriel, Abdullah Ahmed, Ben Said, Mariem, Masmoudi, Saber
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580077/
https://www.ncbi.nlm.nih.gov/pubmed/34514748
http://dx.doi.org/10.1002/mgg3.1810
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author Mosrati, Mohamed Ali
Fadhlaoui‐Zid, Karima
Benammar‐Elgaaied, Amel
Gibriel, Abdullah Ahmed
Ben Said, Mariem
Masmoudi, Saber
author_facet Mosrati, Mohamed Ali
Fadhlaoui‐Zid, Karima
Benammar‐Elgaaied, Amel
Gibriel, Abdullah Ahmed
Ben Said, Mariem
Masmoudi, Saber
author_sort Mosrati, Mohamed Ali
collection PubMed
description Autosomal recessive non‐syndromic hearing loss (ARNSHL) is the most common inherited sensory impairment. It is particularly frequent in North African populations who have a high rate of consanguineous marriage. The c.242G>A homozygous variant in LRTOMT gene was previously established as pathogenic and is associated with NSHL in both humans and mice. The aim of this study is to determine the carrier frequency for the LRTOMT c.242G>A variant and also to estimate its age in addition to evaluating its diagnostic potential as a deafness biomarker among various populations and ethnicities in Northern African countries. A total of 179 Tunisian and 34 Libyan unrelated deafness patients were screened for this variant. The homozygous c.242G>A variant was found in 5.02% and 2.94% in Tunisian and Libyan families, respectively. Subsequent screening for this variant in 263 healthy controls of various ethnicities (136 Tunisian Berbers, 32 Andalusian and 95 Tunisian from undefined ethnic origin) revealed higher frequency for the heterozygous state among Tunisians of Berber origin only (19.11%). Genotyping 7 microsatellite markers nearby the variant location in ARNSHL patients who had the homozygous variant revealed the same haplotype suggesting a common founder origin for this variant. The age of this variant was estimated to be between 2025 and 3425 years (this corresponds to 3400 years when the variant rate was set at 10(−3) or 2600 years when the variant rate is set at 10(−2)), spreading along with the Berber population who migrated to North Africa. In conclusion, the LRTOMT c.242G>A homozygous variant could be used as a useful deafness biomarker for North African ARNSHL patients meanwhile the heterozygous variant could be utilized in genealogical studies for tracing those of the Berber ethnic group.
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spelling pubmed-85800772021-11-17 Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies Mosrati, Mohamed Ali Fadhlaoui‐Zid, Karima Benammar‐Elgaaied, Amel Gibriel, Abdullah Ahmed Ben Said, Mariem Masmoudi, Saber Mol Genet Genomic Med Original Articles Autosomal recessive non‐syndromic hearing loss (ARNSHL) is the most common inherited sensory impairment. It is particularly frequent in North African populations who have a high rate of consanguineous marriage. The c.242G>A homozygous variant in LRTOMT gene was previously established as pathogenic and is associated with NSHL in both humans and mice. The aim of this study is to determine the carrier frequency for the LRTOMT c.242G>A variant and also to estimate its age in addition to evaluating its diagnostic potential as a deafness biomarker among various populations and ethnicities in Northern African countries. A total of 179 Tunisian and 34 Libyan unrelated deafness patients were screened for this variant. The homozygous c.242G>A variant was found in 5.02% and 2.94% in Tunisian and Libyan families, respectively. Subsequent screening for this variant in 263 healthy controls of various ethnicities (136 Tunisian Berbers, 32 Andalusian and 95 Tunisian from undefined ethnic origin) revealed higher frequency for the heterozygous state among Tunisians of Berber origin only (19.11%). Genotyping 7 microsatellite markers nearby the variant location in ARNSHL patients who had the homozygous variant revealed the same haplotype suggesting a common founder origin for this variant. The age of this variant was estimated to be between 2025 and 3425 years (this corresponds to 3400 years when the variant rate was set at 10(−3) or 2600 years when the variant rate is set at 10(−2)), spreading along with the Berber population who migrated to North Africa. In conclusion, the LRTOMT c.242G>A homozygous variant could be used as a useful deafness biomarker for North African ARNSHL patients meanwhile the heterozygous variant could be utilized in genealogical studies for tracing those of the Berber ethnic group. John Wiley and Sons Inc. 2021-09-13 /pmc/articles/PMC8580077/ /pubmed/34514748 http://dx.doi.org/10.1002/mgg3.1810 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Mosrati, Mohamed Ali
Fadhlaoui‐Zid, Karima
Benammar‐Elgaaied, Amel
Gibriel, Abdullah Ahmed
Ben Said, Mariem
Masmoudi, Saber
Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
title Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
title_full Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
title_fullStr Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
title_full_unstemmed Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
title_short Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
title_sort deep analysis of the lrtomtc.242g>a variant in non‐syndromic hearing loss north african patients and the berber population: implications for genetic diagnosis and genealogical studies
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580077/
https://www.ncbi.nlm.nih.gov/pubmed/34514748
http://dx.doi.org/10.1002/mgg3.1810
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