A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non‐Syndromic Hearing Loss
ABSTRACT Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The ad...
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creator | Kazemi, Negar Rezvani Rezvandeh, Raziye Zare Ashrafi, Farzane Shokouhian, Ebrahim Edizadeh, Masoud Booth, Kevin T. A. Kahrizi, Kimia Najmabadi, Hossein Mohseni, Marzieh |
description | ABSTRACT
Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next‐generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants. Despite this, much remains to be uncovered about the genetic basis of sensorineural hearing loss (SNHL). Here, we report an Iranian consanguineous family with postlingual, moderate‐to‐severe autosomal recessive SNHL. After first excluding plausible variants in known deafness‐causing genes using whole exome sequencing, we reanalyzed the data, using a gene/variant prioritization pipeline established for novel gene discovery for HL. This approach identified a novel homozygous frameshift variant c.1934_1937del; (p.Thr645Lysfs*52) in ANKRD24, which segregated with the HL phenotype in the family. Recently, ANKRD24 has been shown to be a pivotal constituent of the stereocilia rootlet in cochlea hair cells and interacts with TRIOBP, a protein already implicated in human deafness. Our data implicate for the first time, ANKRD24 in human nonsyndromic HL (NSHL) and expands the genetic spectrum of HL.
This case report identified a homozygous frameshift variant of ANKRD24 as a novel gene associated with nonsyndromic hearing loss (NHSL) in a consanguineous Iranian family. ANKRD24 is expressed in the stereocilia rootlets in inner ear hair cells, and the encoded protein interacts with TRIOBP, which is a known deafness‐causing gene. |
doi_str_mv | 10.1111/cge.14635 |
format | Article |
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Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next‐generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants. Despite this, much remains to be uncovered about the genetic basis of sensorineural hearing loss (SNHL). Here, we report an Iranian consanguineous family with postlingual, moderate‐to‐severe autosomal recessive SNHL. After first excluding plausible variants in known deafness‐causing genes using whole exome sequencing, we reanalyzed the data, using a gene/variant prioritization pipeline established for novel gene discovery for HL. This approach identified a novel homozygous frameshift variant c.1934_1937del; (p.Thr645Lysfs*52) in ANKRD24, which segregated with the HL phenotype in the family. Recently, ANKRD24 has been shown to be a pivotal constituent of the stereocilia rootlet in cochlea hair cells and interacts with TRIOBP, a protein already implicated in human deafness. Our data implicate for the first time, ANKRD24 in human nonsyndromic HL (NSHL) and expands the genetic spectrum of HL.
This case report identified a homozygous frameshift variant of ANKRD24 as a novel gene associated with nonsyndromic hearing loss (NHSL) in a consanguineous Iranian family. ANKRD24 is expressed in the stereocilia rootlets in inner ear hair cells, and the encoded protein interacts with TRIOBP, which is a known deafness‐causing gene.</description><identifier>ISSN: 0009-9163</identifier><identifier>ISSN: 1399-0004</identifier><identifier>EISSN: 1399-0004</identifier><identifier>DOI: 10.1111/cge.14635</identifier><identifier>PMID: 39434538</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>ANKRD24 ; Child ; Cochlea ; Consanguinity ; Deafness ; Exome Sequencing ; Female ; Frameshift Mutation - genetics ; Genes ; Genetic factors ; Genetic Predisposition to Disease ; Genetic screening ; Hair cells ; Hearing loss ; Hearing Loss, Sensorineural - genetics ; Hearing Loss, Sensorineural - pathology ; High-Throughput Nucleotide Sequencing ; Homozygote ; Humans ; Iran ; Male ; Neonates ; non‐syndromic hearing loss ; novel gene ; Pedigree ; Phenotype ; Phenotypes ; whole exome sequencing ; Whole genome sequencing</subject><ispartof>Clinical genetics, 2025-02, Vol.107 (2), p.214-218</ispartof><rights>2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2435-28fa601390caae5da578ddf8a6e82e7040ab87b7c943413bbfb2b23e7a1ea2cd3</cites><orcidid>0000-0002-6587-7706 ; 0000-0003-1200-4044 ; 0000-0002-6084-7778 ; 0000-0001-9139-9632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcge.14635$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcge.14635$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39434538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kazemi, Negar</creatorcontrib><creatorcontrib>Rezvani Rezvandeh, Raziye</creatorcontrib><creatorcontrib>Zare Ashrafi, Farzane</creatorcontrib><creatorcontrib>Shokouhian, Ebrahim</creatorcontrib><creatorcontrib>Edizadeh, Masoud</creatorcontrib><creatorcontrib>Booth, Kevin T. A.</creatorcontrib><creatorcontrib>Kahrizi, Kimia</creatorcontrib><creatorcontrib>Najmabadi, Hossein</creatorcontrib><creatorcontrib>Mohseni, Marzieh</creatorcontrib><title>A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non‐Syndromic Hearing Loss</title><title>Clinical genetics</title><addtitle>Clin Genet</addtitle><description>ABSTRACT
Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next‐generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants. Despite this, much remains to be uncovered about the genetic basis of sensorineural hearing loss (SNHL). Here, we report an Iranian consanguineous family with postlingual, moderate‐to‐severe autosomal recessive SNHL. After first excluding plausible variants in known deafness‐causing genes using whole exome sequencing, we reanalyzed the data, using a gene/variant prioritization pipeline established for novel gene discovery for HL. This approach identified a novel homozygous frameshift variant c.1934_1937del; (p.Thr645Lysfs*52) in ANKRD24, which segregated with the HL phenotype in the family. Recently, ANKRD24 has been shown to be a pivotal constituent of the stereocilia rootlet in cochlea hair cells and interacts with TRIOBP, a protein already implicated in human deafness. Our data implicate for the first time, ANKRD24 in human nonsyndromic HL (NSHL) and expands the genetic spectrum of HL.
This case report identified a homozygous frameshift variant of ANKRD24 as a novel gene associated with nonsyndromic hearing loss (NHSL) in a consanguineous Iranian family. ANKRD24 is expressed in the stereocilia rootlets in inner ear hair cells, and the encoded protein interacts with TRIOBP, which is a known deafness‐causing gene.</description><subject>ANKRD24</subject><subject>Child</subject><subject>Cochlea</subject><subject>Consanguinity</subject><subject>Deafness</subject><subject>Exome Sequencing</subject><subject>Female</subject><subject>Frameshift Mutation - genetics</subject><subject>Genes</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic screening</subject><subject>Hair cells</subject><subject>Hearing loss</subject><subject>Hearing Loss, Sensorineural - genetics</subject><subject>Hearing Loss, Sensorineural - pathology</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Iran</subject><subject>Male</subject><subject>Neonates</subject><subject>non‐syndromic hearing loss</subject><subject>novel gene</subject><subject>Pedigree</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>whole exome sequencing</subject><subject>Whole genome sequencing</subject><issn>0009-9163</issn><issn>1399-0004</issn><issn>1399-0004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKAzEUhoMotlYXvoAE3Ohi2mSSdGaWpfaGpUK9gKshkzlTp8ylJjNIdz6Cz-iTmDrVhWCyOIR8fPznR-icki61p6dW0KW8z8QBalMWBA4hhB-ith2BE9A-a6ETY9b2yTwRHKMWCzjjgvlt9DzAYy1zMC9pUuEnqVNZVDgt8GBxu7xxOZ7lmyxVsgKDZ5XByzKD3fe0zmWBF2Xx-f5xvy1iXeapwlOwgmKF56Uxp-gokZmBs_3soMfx6GE4deZ3k9lwMHeUy5lwXD-RfWJTEyUliFgKz4_jxJd98F3wCCcy8r3IU7vIlEVRErmRy8CTFKSrYtZBV413o8vXGkwV5qlRkGWygLI2IaM0sJfwwKKXf9B1WevCprOU4IJ6jHFLXTeU0nYNDUm40Wku9TakJNz1Hdq-w---LXuxN9ZRDvEv-VOwBXoN8JZmsP3fFA4no0b5BeoEiFA</recordid><startdate>202502</startdate><enddate>202502</enddate><creator>Kazemi, Negar</creator><creator>Rezvani Rezvandeh, Raziye</creator><creator>Zare Ashrafi, Farzane</creator><creator>Shokouhian, Ebrahim</creator><creator>Edizadeh, Masoud</creator><creator>Booth, Kevin T. A.</creator><creator>Kahrizi, Kimia</creator><creator>Najmabadi, Hossein</creator><creator>Mohseni, Marzieh</creator><general>Blackwell Publishing Ltd</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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6587-7706</orcidid><orcidid>https://orcid.org/0000-0003-1200-4044</orcidid><orcidid>https://orcid.org/0000-0002-6084-7778</orcidid><orcidid>https://orcid.org/0000-0001-9139-9632</orcidid></search><sort><creationdate>202502</creationdate><title>A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non‐Syndromic Hearing Loss</title><author>Kazemi, Negar ; Rezvani Rezvandeh, Raziye ; Zare Ashrafi, Farzane ; Shokouhian, Ebrahim ; Edizadeh, Masoud ; Booth, Kevin T. A. ; Kahrizi, Kimia ; Najmabadi, Hossein ; Mohseni, Marzieh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2435-28fa601390caae5da578ddf8a6e82e7040ab87b7c943413bbfb2b23e7a1ea2cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>ANKRD24</topic><topic>Child</topic><topic>Cochlea</topic><topic>Consanguinity</topic><topic>Deafness</topic><topic>Exome Sequencing</topic><topic>Female</topic><topic>Frameshift Mutation - genetics</topic><topic>Genes</topic><topic>Genetic factors</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic screening</topic><topic>Hair cells</topic><topic>Hearing loss</topic><topic>Hearing Loss, Sensorineural - genetics</topic><topic>Hearing Loss, Sensorineural - pathology</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Iran</topic><topic>Male</topic><topic>Neonates</topic><topic>non‐syndromic hearing loss</topic><topic>novel gene</topic><topic>Pedigree</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>whole exome sequencing</topic><topic>Whole genome sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kazemi, Negar</creatorcontrib><creatorcontrib>Rezvani Rezvandeh, Raziye</creatorcontrib><creatorcontrib>Zare Ashrafi, Farzane</creatorcontrib><creatorcontrib>Shokouhian, Ebrahim</creatorcontrib><creatorcontrib>Edizadeh, Masoud</creatorcontrib><creatorcontrib>Booth, Kevin T. A.</creatorcontrib><creatorcontrib>Kahrizi, Kimia</creatorcontrib><creatorcontrib>Najmabadi, Hossein</creatorcontrib><creatorcontrib>Mohseni, Marzieh</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kazemi, Negar</au><au>Rezvani Rezvandeh, Raziye</au><au>Zare Ashrafi, Farzane</au><au>Shokouhian, Ebrahim</au><au>Edizadeh, Masoud</au><au>Booth, Kevin T. A.</au><au>Kahrizi, Kimia</au><au>Najmabadi, Hossein</au><au>Mohseni, Marzieh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non‐Syndromic Hearing Loss</atitle><jtitle>Clinical genetics</jtitle><addtitle>Clin Genet</addtitle><date>2025-02</date><risdate>2025</risdate><volume>107</volume><issue>2</issue><spage>214</spage><epage>218</epage><pages>214-218</pages><issn>0009-9163</issn><issn>1399-0004</issn><eissn>1399-0004</eissn><abstract>ABSTRACT
Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next‐generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants. Despite this, much remains to be uncovered about the genetic basis of sensorineural hearing loss (SNHL). Here, we report an Iranian consanguineous family with postlingual, moderate‐to‐severe autosomal recessive SNHL. After first excluding plausible variants in known deafness‐causing genes using whole exome sequencing, we reanalyzed the data, using a gene/variant prioritization pipeline established for novel gene discovery for HL. This approach identified a novel homozygous frameshift variant c.1934_1937del; (p.Thr645Lysfs*52) in ANKRD24, which segregated with the HL phenotype in the family. Recently, ANKRD24 has been shown to be a pivotal constituent of the stereocilia rootlet in cochlea hair cells and interacts with TRIOBP, a protein already implicated in human deafness. Our data implicate for the first time, ANKRD24 in human nonsyndromic HL (NSHL) and expands the genetic spectrum of HL.
This case report identified a homozygous frameshift variant of ANKRD24 as a novel gene associated with nonsyndromic hearing loss (NHSL) in a consanguineous Iranian family. ANKRD24 is expressed in the stereocilia rootlets in inner ear hair cells, and the encoded protein interacts with TRIOBP, which is a known deafness‐causing gene.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>39434538</pmid><doi>10.1111/cge.14635</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-6587-7706</orcidid><orcidid>https://orcid.org/0000-0003-1200-4044</orcidid><orcidid>https://orcid.org/0000-0002-6084-7778</orcidid><orcidid>https://orcid.org/0000-0001-9139-9632</orcidid></addata></record> |
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subjects | ANKRD24 Child Cochlea Consanguinity Deafness Exome Sequencing Female Frameshift Mutation - genetics Genes Genetic factors Genetic Predisposition to Disease Genetic screening Hair cells Hearing loss Hearing Loss, Sensorineural - genetics Hearing Loss, Sensorineural - pathology High-Throughput Nucleotide Sequencing Homozygote Humans Iran Male Neonates non‐syndromic hearing loss novel gene Pedigree Phenotype Phenotypes whole exome sequencing Whole genome sequencing |
title | A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non‐Syndromic Hearing Loss |
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