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Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness
MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate...
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Published in: | BMC medical genetics 2018-02, Vol.19 (1), p.29-29, Article 29 |
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description | MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness.
Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.
In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants.
Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation. |
doi_str_mv | 10.1186/s12881-018-0541-9 |
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Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.
In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants.
Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.</description><identifier>ISSN: 1471-2350</identifier><identifier>EISSN: 1471-2350</identifier><identifier>DOI: 10.1186/s12881-018-0541-9</identifier><identifier>PMID: 29482514</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Alleles ; Amino Acid Sequence ; Analysis ; Asian Continental Ancestry Group - genetics ; Cochlear Implantation ; Complications and side effects ; Deafness ; Exome ; Genes, Recessive ; Genetic disorders ; Hearing Loss, Sensorineural - genetics ; Humans ; Molecular genetics ; MYO15A ; Myosins - genetics ; Pathogenic variant ; Pedigree ; Phenotype ; Polymorphism, Single Nucleotide ; Risk factors ; Whole Exome Sequencing</subject><ispartof>BMC medical genetics, 2018-02, Vol.19 (1), p.29-29, Article 29</ispartof><rights>COPYRIGHT 2018 BioMed Central Ltd.</rights><rights>The Author(s). 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c632t-2d0e742498c5992652201ddb3eb994892dff659ddeadce8773b46c33c9cf5d653</citedby><cites>FETCH-LOGICAL-c632t-2d0e742498c5992652201ddb3eb994892dff659ddeadce8773b46c33c9cf5d653</cites><orcidid>0000-0001-5125-2118</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389081/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389081/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,37013,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29482514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Mun Young</creatorcontrib><creatorcontrib>Lee, Chung</creatorcontrib><creatorcontrib>Han, Jin Hee</creatorcontrib><creatorcontrib>Kim, Min Young</creatorcontrib><creatorcontrib>Park, Hye-Rim</creatorcontrib><creatorcontrib>Kim, Nayoung</creatorcontrib><creatorcontrib>Park, Woong-Yang</creatorcontrib><creatorcontrib>Oh, Doo Yi</creatorcontrib><creatorcontrib>Choi, Byung Yoon</creatorcontrib><title>Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness</title><title>BMC medical genetics</title><addtitle>BMC Med Genet</addtitle><description>MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness.
Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.
In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants.
Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.</description><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Analysis</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Cochlear Implantation</subject><subject>Complications and side effects</subject><subject>Deafness</subject><subject>Exome</subject><subject>Genes, Recessive</subject><subject>Genetic disorders</subject><subject>Hearing Loss, Sensorineural - genetics</subject><subject>Humans</subject><subject>Molecular genetics</subject><subject>MYO15A</subject><subject>Myosins - genetics</subject><subject>Pathogenic variant</subject><subject>Pedigree</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk factors</subject><subject>Whole Exome Sequencing</subject><issn>1471-2350</issn><issn>1471-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptkktr3DAURk1paR7tD-imGLppF071tKVNYQhpO5AS6GPRlZD18Ch4JFeSh4T--ciZNGSgeCFz77lHD76qegPBGYSs_ZggYgw2ALIGUAIb_qw6hqSDDcIUPH_yf1SdpHQNAOwYxi-rI8QJQxSS4-rvxc0kfXLB18HW08b4kG8np-o0GZXjvF3K335fQbqqJ5k3YTC-dHcyOulzqnOonVfjrE09hZRH54dZjnXwyeR7YwxDNCm5XQFkzK40tZHWl9qr6oWVYzKvH9bT6tfni5_nX5vLqy_r89Vlo1qMcoM0MB1BhDNFOUctRQhArXtsel7uwZG2tqVcF61WhnUd7kmrMFZcWapbik-r9d6rg7wWU3RbGW9FkE7cF0IcxHIyNRoBueKk57jDtiOt1RIbAKhU2CpiLe2L69PeNc391pT9fI5yPJAedrzbiCHsRIsZBwwWwfsHQQx_ZpOy2LqkzDhKb8KcBAKAMUYwWtB3e3SQ5WjO21CMasHFipIWsI6TrlBn_6HKp83WqeCNdaV-MPDhYKAw2dzkQc4pifWP74cs3LMqhpSisY83hUAsGRT7DIqSQbFkUPAy8_bpEz1O_AsdvgNka9ic</recordid><startdate>20180227</startdate><enddate>20180227</enddate><creator>Chang, Mun Young</creator><creator>Lee, Chung</creator><creator>Han, Jin Hee</creator><creator>Kim, Min Young</creator><creator>Park, Hye-Rim</creator><creator>Kim, Nayoung</creator><creator>Park, Woong-Yang</creator><creator>Oh, Doo Yi</creator><creator>Choi, Byung Yoon</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5125-2118</orcidid></search><sort><creationdate>20180227</creationdate><title>Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness</title><author>Chang, Mun Young ; Lee, Chung ; Han, Jin Hee ; Kim, Min Young ; Park, Hye-Rim ; Kim, Nayoung ; Park, Woong-Yang ; Oh, Doo Yi ; Choi, Byung Yoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c632t-2d0e742498c5992652201ddb3eb994892dff659ddeadce8773b46c33c9cf5d653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Analysis</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Cochlear Implantation</topic><topic>Complications and side effects</topic><topic>Deafness</topic><topic>Exome</topic><topic>Genes, Recessive</topic><topic>Genetic disorders</topic><topic>Hearing Loss, Sensorineural - genetics</topic><topic>Humans</topic><topic>Molecular genetics</topic><topic>MYO15A</topic><topic>Myosins - genetics</topic><topic>Pathogenic variant</topic><topic>Pedigree</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk factors</topic><topic>Whole Exome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Mun Young</creatorcontrib><creatorcontrib>Lee, Chung</creatorcontrib><creatorcontrib>Han, Jin Hee</creatorcontrib><creatorcontrib>Kim, Min Young</creatorcontrib><creatorcontrib>Park, Hye-Rim</creatorcontrib><creatorcontrib>Kim, Nayoung</creatorcontrib><creatorcontrib>Park, Woong-Yang</creatorcontrib><creatorcontrib>Oh, Doo Yi</creatorcontrib><creatorcontrib>Choi, Byung Yoon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>BMC medical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Mun Young</au><au>Lee, Chung</au><au>Han, Jin Hee</au><au>Kim, Min Young</au><au>Park, Hye-Rim</au><au>Kim, Nayoung</au><au>Park, Woong-Yang</au><au>Oh, Doo Yi</au><au>Choi, Byung Yoon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness</atitle><jtitle>BMC medical genetics</jtitle><addtitle>BMC Med Genet</addtitle><date>2018-02-27</date><risdate>2018</risdate><volume>19</volume><issue>1</issue><spage>29</spage><epage>29</epage><pages>29-29</pages><artnum>29</artnum><issn>1471-2350</issn><eissn>1471-2350</eissn><abstract>MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness.
Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.
In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants.
Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>29482514</pmid><doi>10.1186/s12881-018-0541-9</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5125-2118</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Alleles Amino Acid Sequence Analysis Asian Continental Ancestry Group - genetics Cochlear Implantation Complications and side effects Deafness Exome Genes, Recessive Genetic disorders Hearing Loss, Sensorineural - genetics Humans Molecular genetics MYO15A Myosins - genetics Pathogenic variant Pedigree Phenotype Polymorphism, Single Nucleotide Risk factors Whole Exome Sequencing |
title | Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness |
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