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

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mohamed Ali Mosrati, Karima Fadhlaoui‐Zid, Amel Benammar‐Elgaaied, Abdullah Ahmed Gibriel, Mariem Ben Said, Saber Masmoudi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Arg81Gln Berber and Biomarkers DFNB63 LRTOMT Genetics QH426-470
Acceso en línea:	https://doaj.org/article/29daf1cf4ebf4f7b903815af2e77e718
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:29daf1cf4ebf4f7b903815af2e77e718
record_format	dspace
spelling	oai:doaj.org-article:29daf1cf4ebf4f7b903815af2e77e7182021-11-10T16:39:24ZDeep 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 studies2324-926910.1002/mgg3.1810https://doaj.org/article/29daf1cf4ebf4f7b903815af2e77e7182021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1810https://doaj.org/toc/2324-9269Abstract 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.Mohamed Ali MosratiKarima Fadhlaoui‐ZidAmel Benammar‐ElgaaiedAbdullah Ahmed GibrielMariem Ben SaidSaber MasmoudiWileyarticleArg81GlnBerber and BiomarkersDFNB63LRTOMTGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arg81Gln Berber and Biomarkers DFNB63 LRTOMT Genetics QH426-470
spellingShingle	Arg81Gln Berber and Biomarkers DFNB63 LRTOMT Genetics QH426-470 Mohamed Ali Mosrati Karima Fadhlaoui‐Zid Amel Benammar‐Elgaaied Abdullah Ahmed Gibriel Mariem Ben Said Saber Masmoudi 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
description	Abstract 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.
format	article
author	Mohamed Ali Mosrati Karima Fadhlaoui‐Zid Amel Benammar‐Elgaaied Abdullah Ahmed Gibriel Mariem Ben Said Saber Masmoudi
author_facet	Mohamed Ali Mosrati Karima Fadhlaoui‐Zid Amel Benammar‐Elgaaied Abdullah Ahmed Gibriel Mariem Ben Said Saber Masmoudi
author_sort	Mohamed Ali Mosrati
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_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_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_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
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/29daf1cf4ebf4f7b903815af2e77e718
work_keys_str_mv	AT mohamedalimosrati deepanalysisofthelrtomtc242gavariantinnonsyndromichearinglossnorthafricanpatientsandtheberberpopulationimplicationsforgeneticdiagnosisandgenealogicalstudies AT karimafadhlaouizid deepanalysisofthelrtomtc242gavariantinnonsyndromichearinglossnorthafricanpatientsandtheberberpopulationimplicationsforgeneticdiagnosisandgenealogicalstudies AT amelbenammarelgaaied deepanalysisofthelrtomtc242gavariantinnonsyndromichearinglossnorthafricanpatientsandtheberberpopulationimplicationsforgeneticdiagnosisandgenealogicalstudies AT abdullahahmedgibriel deepanalysisofthelrtomtc242gavariantinnonsyndromichearinglossnorthafricanpatientsandtheberberpopulationimplicationsforgeneticdiagnosisandgenealogicalstudies AT mariembensaid deepanalysisofthelrtomtc242gavariantinnonsyndromichearinglossnorthafricanpatientsandtheberberpopulationimplicationsforgeneticdiagnosisandgenealogicalstudies AT sabermasmoudi deepanalysisofthelrtomtc242gavariantinnonsyndromichearinglossnorthafricanpatientsandtheberberpopulationimplicationsforgeneticdiagnosisandgenealogicalstudies
_version_	1718439853328171008

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

Ejemplares similares