Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health
Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1384094/full |
| _version_ | 1797197772178325504 |
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| author | Rahma Mkaouar Zied Riahi Jihene Marrakchi Jihene Marrakchi Nessrine Mezzi Nessrine Mezzi Lilia Romdhane Lilia Romdhane Maroua Boujemaa Hamza Dallali Hamza Dallali Marwa Sayeb Saida Lahbib Hager Jaouadi Hager Jaouadi Hela Boudabbous Hela Boudabbous Hela Boudabbous Lotfi Zekri Lotfi Zekri Mariem Chargui Olfa Messaoud Meriem Elyounsi Meriem Elyounsi Ichraf Kraoua Ichraf Kraoua Anissa Zaouak Ilhem Turki Ilhem Turki Mourad Mokni Sophie Boucher Sophie Boucher Christine Petit Christine Petit Fabrice Giraudet Fabrice Giraudet Chiraz Mbarek Ghazi Besbes Soumeyya Halayem Soumeyya Halayem Rim Zainine Rim Zainine Hamida Turki Amel Tounsi Crystel Bonnet Ridha Mrad Ridha Mrad Sonia Abdelhak Mediha Trabelsi Mediha Trabelsi Cherine Charfeddine |
| author_facet | Rahma Mkaouar Zied Riahi Jihene Marrakchi Jihene Marrakchi Nessrine Mezzi Nessrine Mezzi Lilia Romdhane Lilia Romdhane Maroua Boujemaa Hamza Dallali Hamza Dallali Marwa Sayeb Saida Lahbib Hager Jaouadi Hager Jaouadi Hela Boudabbous Hela Boudabbous Hela Boudabbous Lotfi Zekri Lotfi Zekri Mariem Chargui Olfa Messaoud Meriem Elyounsi Meriem Elyounsi Ichraf Kraoua Ichraf Kraoua Anissa Zaouak Ilhem Turki Ilhem Turki Mourad Mokni Sophie Boucher Sophie Boucher Christine Petit Christine Petit Fabrice Giraudet Fabrice Giraudet Chiraz Mbarek Ghazi Besbes Soumeyya Halayem Soumeyya Halayem Rim Zainine Rim Zainine Hamida Turki Amel Tounsi Crystel Bonnet Ridha Mrad Ridha Mrad Sonia Abdelhak Mediha Trabelsi Mediha Trabelsi Cherine Charfeddine |
| author_sort | Rahma Mkaouar |
| collection | DOAJ |
| description | Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007–2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice. |
| first_indexed | 2024-04-24T06:49:16Z |
| format | Article |
| id | doaj.art-d53f3da42b5b4e8f9503ec02796dd375 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-24T06:49:16Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d53f3da42b5b4e8f9503ec02796dd3752024-04-22T14:19:33ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-04-011510.3389/fgene.2024.13840941384094Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory healthRahma Mkaouar0Zied Riahi1Jihene Marrakchi2Jihene Marrakchi3Nessrine Mezzi4Nessrine Mezzi5Lilia Romdhane6Lilia Romdhane7Maroua Boujemaa8Hamza Dallali9Hamza Dallali10Marwa Sayeb11Saida Lahbib12Hager Jaouadi13Hager Jaouadi14Hela Boudabbous15Hela Boudabbous16Hela Boudabbous17Lotfi Zekri18Lotfi Zekri19Mariem Chargui20Olfa Messaoud21Meriem Elyounsi22Meriem Elyounsi23Ichraf Kraoua24Ichraf Kraoua25Anissa Zaouak26Ilhem Turki27Ilhem Turki28Mourad Mokni29Sophie Boucher30Sophie Boucher31Christine Petit32Christine Petit33Fabrice Giraudet34Fabrice Giraudet35Chiraz Mbarek36Ghazi Besbes37Soumeyya Halayem38Soumeyya Halayem39Rim Zainine40Rim Zainine41Hamida Turki42Amel Tounsi43Crystel Bonnet44Ridha Mrad45Ridha Mrad46Sonia Abdelhak47Mediha Trabelsi48Mediha Trabelsi49Cherine Charfeddine50Laboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Otorhinolaryngology, District Hospital of Menzel Bourguiba, Bizerte, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Biology, Faculty of Sciences of Bizerte, Université Tunis Carthage, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Biology, Faculty of Sciences of Bizerte, Université Tunis Carthage, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaGenetic Typing Service, Institut Pasteur of Tunis, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaMarseille Medical Genetics (MMG) U1251, Aix Marseille Université, INSERM, Marseille, FranceDepartment of Pediatrics, La Rabta Hospital, Tunis, TunisiaLaboratory of Hereditary Diseases of the Metabolism Investigation and Patients Management, Faculty of Medicine in Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Epidemiology and Public Health, Directorate General of Military Health, Faculty of Medicine in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaICHARA Association (International Research Institute on Sign Language), Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, Tunisia0Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital in Tunis, Tunis, Tunisia1LR99ES10 Laboratory of Human Genetics, Faculty of Medicine in Tunis, University of Tunis El Manar, Tunis, Tunisia2Child and Adolescent Neurology Department of Neurology, National Institute of Neurology, Tunis, Tunisia3LR18SP04 Department of Child Neurology, National Institute Mongi Ben Hmida of Neurology in Tunis. University of Tunis El Manar, Tunis, Tunisia4Department of Dermatology, Habib Thameur Hospital, Research Unit Genodermatoses and Cancers LR12SP03, Tunis, Tunisia2Child and Adolescent Neurology Department of Neurology, National Institute of Neurology, Tunis, Tunisia3LR18SP04 Department of Child Neurology, National Institute Mongi Ben Hmida of Neurology in Tunis. University of Tunis El Manar, Tunis, Tunisia5Service de dermatologie, Hôpital La Rabta, Unité de recherche UR 12SP07, Hôpital La Rabta, Tunis, Tunisia6Service d’ORL et chirurgie cervico-faciale, CHU d’Angers, Angers, France7Equipe Mitolab, Institut Mitovasc, CNRS UMR6015, UMR Inserm 1083, Université d’Angers, Angers, France8Institut Pasteur, Université Paris Cité, Inserm UA06, Institut de l’Audition, Paris, France9Collège de France, Paris, France0Unité Mixte de Recherche (UMR) 1107, INSERM, Clermont-Ferrand, France1Centre Auditif SoluSons, Clermont-Ferrand, France2ENT Department, Habib Thameur Hospital, Tunis, Tunisia3Department of Otorhinolaryngology and Maxillofacial Surgery - La Rabta Hospital in Tunis, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, Tunisia4Service de pédopsychiatrie, Hôpital Razi, Faculté de Médecine de Tunis, Université Tunis el Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, Tunisia3Department of Otorhinolaryngology and Maxillofacial Surgery - La Rabta Hospital in Tunis, Tunis, Tunisia5Dermatology Department Hedi Chaker University Hospital, Sfax University Sfax Tunisia, Tunis, Tunisia6CNSS Polyclinic, Bizerte, Tunisia8Institut Pasteur, Université Paris Cité, Inserm UA06, Institut de l’Audition, Paris, France0Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital in Tunis, Tunis, Tunisia1LR99ES10 Laboratory of Human Genetics, Faculty of Medicine in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, Tunisia0Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital in Tunis, Tunis, Tunisia1LR99ES10 Laboratory of Human Genetics, Faculty of Medicine in Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Biomedical Genomics and Oncogenetics LR16IPT05, Pasteur Institute in Tunis, University of Tunis El Manar, Tunis, TunisiaHearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007–2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice.https://www.frontiersin.org/articles/10.3389/fgene.2024.1384094/fullsyndromic deafness (SD)spectrum of SDsnext-generation sequencing (NGS)early detectionunder-diagnosisTunisia |
| spellingShingle | Rahma Mkaouar Zied Riahi Jihene Marrakchi Jihene Marrakchi Nessrine Mezzi Nessrine Mezzi Lilia Romdhane Lilia Romdhane Maroua Boujemaa Hamza Dallali Hamza Dallali Marwa Sayeb Saida Lahbib Hager Jaouadi Hager Jaouadi Hela Boudabbous Hela Boudabbous Hela Boudabbous Lotfi Zekri Lotfi Zekri Mariem Chargui Olfa Messaoud Meriem Elyounsi Meriem Elyounsi Ichraf Kraoua Ichraf Kraoua Anissa Zaouak Ilhem Turki Ilhem Turki Mourad Mokni Sophie Boucher Sophie Boucher Christine Petit Christine Petit Fabrice Giraudet Fabrice Giraudet Chiraz Mbarek Ghazi Besbes Soumeyya Halayem Soumeyya Halayem Rim Zainine Rim Zainine Hamida Turki Amel Tounsi Crystel Bonnet Ridha Mrad Ridha Mrad Sonia Abdelhak Mediha Trabelsi Mediha Trabelsi Cherine Charfeddine Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health Frontiers in Genetics syndromic deafness (SD) spectrum of SDs next-generation sequencing (NGS) early detection under-diagnosis Tunisia |
| title | Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health |
| title_full | Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health |
| title_fullStr | Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health |
| title_full_unstemmed | Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health |
| title_short | Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health |
| title_sort | current phenotypic and genetic spectrum of syndromic deafness in tunisia paving the way for precision auditory health |
| topic | syndromic deafness (SD) spectrum of SDs next-generation sequencing (NGS) early detection under-diagnosis Tunisia |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1384094/full |
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