Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families
<p dir="ltr">The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel...
محفوظ في:
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , , , , , , |
| منشور في: |
2020
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إضافة وسم
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| _version_ | 1864513512842199040 |
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| author | Julia Doll (5237840) |
| author2 | Barbara Vona (5237843) Linda Schnapp (18718837) Franz Rüschendorf (73756) Imran Khan (109715) Saadullah Khan (5735540) Noor Muhammad (820180) Sher Alam Khan (18718840) Hamed Nawaz (18718843) Ajmal Khan (358733) Naseer Ahmad (4870411) Susanne M. Kolb (18718846) Laura Kühlewein (18718849) Jonathan D. J. Labonne (18090841) Lawrence C. Layman (13913559) Michaela A. H. Hofrichter (18718852) Tabea Röder (18718855) Marcus Dittrich (167737) Tobias Müller (163591) Tyler D. Graves (18718858) Il-Keun Kong (85884) Indrajit Nanda (226370) Hyung-Goo Kim (728597) Thomas Haaf (342924) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Julia Doll (5237840) Barbara Vona (5237843) Linda Schnapp (18718837) Franz Rüschendorf (73756) Imran Khan (109715) Saadullah Khan (5735540) Noor Muhammad (820180) Sher Alam Khan (18718840) Hamed Nawaz (18718843) Ajmal Khan (358733) Naseer Ahmad (4870411) Susanne M. Kolb (18718846) Laura Kühlewein (18718849) Jonathan D. J. Labonne (18090841) Lawrence C. Layman (13913559) Michaela A. H. Hofrichter (18718852) Tabea Röder (18718855) Marcus Dittrich (167737) Tobias Müller (163591) Tyler D. Graves (18718858) Il-Keun Kong (85884) Indrajit Nanda (226370) Hyung-Goo Kim (728597) Thomas Haaf (342924) |
| author_role | author |
| dc.creator.none.fl_str_mv | Julia Doll (5237840) Barbara Vona (5237843) Linda Schnapp (18718837) Franz Rüschendorf (73756) Imran Khan (109715) Saadullah Khan (5735540) Noor Muhammad (820180) Sher Alam Khan (18718840) Hamed Nawaz (18718843) Ajmal Khan (358733) Naseer Ahmad (4870411) Susanne M. Kolb (18718846) Laura Kühlewein (18718849) Jonathan D. J. Labonne (18090841) Lawrence C. Layman (13913559) Michaela A. H. Hofrichter (18718852) Tabea Röder (18718855) Marcus Dittrich (167737) Tobias Müller (163591) Tyler D. Graves (18718858) Il-Keun Kong (85884) Indrajit Nanda (226370) Hyung-Goo Kim (728597) Thomas Haaf (342924) |
| dc.date.none.fl_str_mv | 2020-11-11T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/genes11111329 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genetic_Spectrum_of_Syndromic_and_Non-Syndromic_Hearing_Loss_in_Pakistani_Families/25958086 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences genetic diagnosis consanguinity genome-wide linkage analysis hearing loss Pakistan exome sequencing |
| dc.title.none.fl_str_mv | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.</p><h2>Other Information</h2><p dir="ltr">Published in: Genes<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/genes11111329" target="_blank">https://dx.doi.org/10.3390/genes11111329</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_53b5247dce76392bc4b392eb725f4375 |
| identifier_str_mv | 10.3390/genes11111329 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25958086 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani FamiliesJulia Doll (5237840)Barbara Vona (5237843)Linda Schnapp (18718837)Franz Rüschendorf (73756)Imran Khan (109715)Saadullah Khan (5735540)Noor Muhammad (820180)Sher Alam Khan (18718840)Hamed Nawaz (18718843)Ajmal Khan (358733)Naseer Ahmad (4870411)Susanne M. Kolb (18718846)Laura Kühlewein (18718849)Jonathan D. J. Labonne (18090841)Lawrence C. Layman (13913559)Michaela A. H. Hofrichter (18718852)Tabea Röder (18718855)Marcus Dittrich (167737)Tobias Müller (163591)Tyler D. Graves (18718858)Il-Keun Kong (85884)Indrajit Nanda (226370)Hyung-Goo Kim (728597)Thomas Haaf (342924)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesNeurosciencesgenetic diagnosisconsanguinitygenome-wide linkage analysishearing lossPakistanexome sequencing<p dir="ltr">The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.</p><h2>Other Information</h2><p dir="ltr">Published in: Genes<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/genes11111329" target="_blank">https://dx.doi.org/10.3390/genes11111329</a></p>2020-11-11T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/genes11111329https://figshare.com/articles/journal_contribution/Genetic_Spectrum_of_Syndromic_and_Non-Syndromic_Hearing_Loss_in_Pakistani_Families/25958086CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259580862020-11-11T09:00:00Z |
| spellingShingle | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families Julia Doll (5237840) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences genetic diagnosis consanguinity genome-wide linkage analysis hearing loss Pakistan exome sequencing |
| status_str | publishedVersion |
| title | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| title_full | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| title_fullStr | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| title_full_unstemmed | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| title_short | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| title_sort | Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences genetic diagnosis consanguinity genome-wide linkage analysis hearing loss Pakistan exome sequencing |