Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF

<h3>Background</h3><p dir="ltr">Hearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1–5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of...

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Main Author: Athar Khalil (5906330) (author)
Other Authors: Samer Bou Karroum (19022876) (author), Rana Barake (7962539) (author), Gabriel Dunya (8213655) (author), Samer Abou-Rizk (8213658) (author), Amina Kamar (295977) (author), Georges Nemer (295984) (author), Marc Bassim (7962545) (author)
Published: 2020
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_version_ 1864513511257800704
author Athar Khalil (5906330)
author2 Samer Bou Karroum (19022876)
Rana Barake (7962539)
Gabriel Dunya (8213655)
Samer Abou-Rizk (8213658)
Amina Kamar (295977)
Georges Nemer (295984)
Marc Bassim (7962545)
author2_role author
author
author
author
author
author
author
author_facet Athar Khalil (5906330)
Samer Bou Karroum (19022876)
Rana Barake (7962539)
Gabriel Dunya (8213655)
Samer Abou-Rizk (8213658)
Amina Kamar (295977)
Georges Nemer (295984)
Marc Bassim (7962545)
author_role author
dc.creator.none.fl_str_mv Athar Khalil (5906330)
Samer Bou Karroum (19022876)
Rana Barake (7962539)
Gabriel Dunya (8213655)
Samer Abou-Rizk (8213658)
Amina Kamar (295977)
Georges Nemer (295984)
Marc Bassim (7962545)
dc.date.none.fl_str_mv 2020-01-02T03:00:00Z
dc.identifier.none.fl_str_mv 10.1186/s12881-019-0942-4
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Post-lingual_non-syndromic_hearing_loss_phenotype_a_polygenic_case_with_2_biallelic_mutations_in_MYO15A_and_MITF/26232455
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
Congenital hearing loss
Non-syndromic hearing loss
MITF
MYO15A
Whole exome sequencing
dc.title.none.fl_str_mv Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">Hearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1–5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of all genetic hearing loss cases.</p><h3>Methods</h3><p dir="ltr">In the current study, we reported a polygenic mode of inheritance in an NSHL consanguineous family using exome sequencing technology and we evaluated the possible effect of the detected single nucleotide variants (SNVs) using in silico methods.</p><h3>Results</h3><p dir="ltr">Two bi-allelic SNVs were detected in the affected patients; a<i> MYO15A</i> (. p.V<sub>4</sub>8<sub>5</sub>A) variant, and a novel <i>MITF</i> (p.P<sub>33</sub>8L) variant. Along with these homozygous mutations, we detected two heterozygous variants in well described hearing loss genes (<i>MYO</i><sub><em>7</em></sub>A and <i>MYH</i><sub>14</sub>). The novel MITF p. Pro<sub>33</sub>8Leu missense mutation was predicted to change the protein structure and function.</p><h3>Conclusion</h3><p dir="ltr">A novel <i>MITF</i> mutation along with a previously described <i>MYO</i><sub><em>15</em></sub><i>A</i> mutation segregate with an autosomal recessive non-syndromic HL case with a post-lingual onset. The findings highlight the importance of carrying whole exome sequencing for a comprehensive assessment of HL genetic heterogeneity.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genetics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12881-019-0942-4" target="_blank">https://dx.doi.org/10.1186/s12881-019-0942-4</a></p>
eu_rights_str_mv openAccess
id Manara2_d10bc08c36133a4d038930f2be0958c4
identifier_str_mv 10.1186/s12881-019-0942-4
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/26232455
publishDate 2020
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repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITFAthar Khalil (5906330)Samer Bou Karroum (19022876)Rana Barake (7962539)Gabriel Dunya (8213655)Samer Abou-Rizk (8213658)Amina Kamar (295977)Georges Nemer (295984)Marc Bassim (7962545)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesCongenital hearing lossNon-syndromic hearing lossMITFMYO15AWhole exome sequencing<h3>Background</h3><p dir="ltr">Hearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1–5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of all genetic hearing loss cases.</p><h3>Methods</h3><p dir="ltr">In the current study, we reported a polygenic mode of inheritance in an NSHL consanguineous family using exome sequencing technology and we evaluated the possible effect of the detected single nucleotide variants (SNVs) using in silico methods.</p><h3>Results</h3><p dir="ltr">Two bi-allelic SNVs were detected in the affected patients; a<i> MYO15A</i> (. p.V<sub>4</sub>8<sub>5</sub>A) variant, and a novel <i>MITF</i> (p.P<sub>33</sub>8L) variant. Along with these homozygous mutations, we detected two heterozygous variants in well described hearing loss genes (<i>MYO</i><sub><em>7</em></sub>A and <i>MYH</i><sub>14</sub>). The novel MITF p. Pro<sub>33</sub>8Leu missense mutation was predicted to change the protein structure and function.</p><h3>Conclusion</h3><p dir="ltr">A novel <i>MITF</i> mutation along with a previously described <i>MYO</i><sub><em>15</em></sub><i>A</i> mutation segregate with an autosomal recessive non-syndromic HL case with a post-lingual onset. The findings highlight the importance of carrying whole exome sequencing for a comprehensive assessment of HL genetic heterogeneity.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genetics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12881-019-0942-4" target="_blank">https://dx.doi.org/10.1186/s12881-019-0942-4</a></p>2020-01-02T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12881-019-0942-4https://figshare.com/articles/journal_contribution/Post-lingual_non-syndromic_hearing_loss_phenotype_a_polygenic_case_with_2_biallelic_mutations_in_MYO15A_and_MITF/26232455CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/262324552020-01-02T03:00:00Z
spellingShingle Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
Athar Khalil (5906330)
Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Congenital hearing loss
Non-syndromic hearing loss
MITF
MYO15A
Whole exome sequencing
status_str publishedVersion
title Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
title_full Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
title_fullStr Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
title_full_unstemmed Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
title_short Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
title_sort Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF
topic Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Congenital hearing loss
Non-syndromic hearing loss
MITF
MYO15A
Whole exome sequencing