The identification of two pathogenic variants in a family with mild and severe forms of developmental delay

Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in pat...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of human genetics 2021-04, Vol.66 (4), p.445-448
Hauptverfasser: Miyake, Noriko, Heydari, Shermineh, Garshasbi, Masoud, Saitoh, Shinji, Nasiri, Jafar, Hamanaka, Kohei, Takata, Atsushi, Matsumoto, Naomichi, Beheshti, Farnaz Hosseini, Chaleshtori, Ahmad Reza Salehi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 448
container_issue 4
container_start_page 445
container_title Journal of human genetics
container_volume 66
creator Miyake, Noriko
Heydari, Shermineh
Garshasbi, Masoud
Saitoh, Shinji
Nasiri, Jafar
Hamanaka, Kohei
Takata, Atsushi
Matsumoto, Naomichi
Beheshti, Farnaz Hosseini
Chaleshtori, Ahmad Reza Salehi
description Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.
doi_str_mv 10.1038/s10038-020-0809-8
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2449957353</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2449957353</sourcerecordid><originalsourceid>FETCH-LOGICAL-c305t-e04522875a8f5f6ff3dc760e7a1b2b0230c5a7c835bb1c0bbabd6c284fc59f403</originalsourceid><addsrcrecordid>eNpdkUtLxDAUhYMoPkZ_gBsJuHFTvUmaNl2K-ALBzQjuQpomTsa2qUmrzL8344wuXJ174NyPyz0InRK4JMDEVSSQJAMKGQioMrGDDknOeEYZfd39mfOMk4IcoKMYl5DStKT76IAxYCWr4BC9zxcGu8b0o7NOq9H5HnuLxy-PBzUu_JvpncafKjjVjxG7HitsVefaFf5y4wKnqcGqb3A0nyYYbH3o4prQJN_6oUtk1SbXqtUx2rOqjeZkqzP0cnc7v3nInp7vH2-unzLNgI-ZgZxTKkquhOW2sJY1uizAlIrUtAbKQHNVasF4XRMNda3qptBU5FbzyubAZuhiwx2C_5hMHGXnojZtq3rjpyhpnlcVLxlnKXr-L7r0U-jTdZJyyAsqeLkGkk1KBx9jMFYOwXUqrCQBuW5CbpqQqQm5bkKKtHO2JU91Z5q_jd_Xs2_Tk4R8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2504628570</pqid></control><display><type>article</type><title>The identification of two pathogenic variants in a family with mild and severe forms of developmental delay</title><source>Alma/SFX Local Collection</source><creator>Miyake, Noriko ; Heydari, Shermineh ; Garshasbi, Masoud ; Saitoh, Shinji ; Nasiri, Jafar ; Hamanaka, Kohei ; Takata, Atsushi ; Matsumoto, Naomichi ; Beheshti, Farnaz Hosseini ; Chaleshtori, Ahmad Reza Salehi</creator><creatorcontrib>Miyake, Noriko ; Heydari, Shermineh ; Garshasbi, Masoud ; Saitoh, Shinji ; Nasiri, Jafar ; Hamanaka, Kohei ; Takata, Atsushi ; Matsumoto, Naomichi ; Beheshti, Farnaz Hosseini ; Chaleshtori, Ahmad Reza Salehi</creatorcontrib><description>Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.</description><identifier>ISSN: 1434-5161</identifier><identifier>EISSN: 1435-232X</identifier><identifier>DOI: 10.1038/s10038-020-0809-8</identifier><identifier>PMID: 33037390</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Disease ; Environmental factors ; Gene deletion ; Genetic analysis ; Genetic diversity ; Genetics ; Genotype &amp; phenotype ; Intellectual disabilities ; KCNQ3 protein ; Parents &amp; parenting ; Patients ; Phenotypes ; Potassium channels (voltage-gated) ; Proteins ; Siblings ; Ubiquitin-protein ligase</subject><ispartof>Journal of human genetics, 2021-04, Vol.66 (4), p.445-448</ispartof><rights>The Author(s), under exclusive licence to The Japan Society of Human Genetics 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c305t-e04522875a8f5f6ff3dc760e7a1b2b0230c5a7c835bb1c0bbabd6c284fc59f403</cites><orcidid>0000-0001-6911-3351</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33037390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyake, Noriko</creatorcontrib><creatorcontrib>Heydari, Shermineh</creatorcontrib><creatorcontrib>Garshasbi, Masoud</creatorcontrib><creatorcontrib>Saitoh, Shinji</creatorcontrib><creatorcontrib>Nasiri, Jafar</creatorcontrib><creatorcontrib>Hamanaka, Kohei</creatorcontrib><creatorcontrib>Takata, Atsushi</creatorcontrib><creatorcontrib>Matsumoto, Naomichi</creatorcontrib><creatorcontrib>Beheshti, Farnaz Hosseini</creatorcontrib><creatorcontrib>Chaleshtori, Ahmad Reza Salehi</creatorcontrib><title>The identification of two pathogenic variants in a family with mild and severe forms of developmental delay</title><title>Journal of human genetics</title><addtitle>J Hum Genet</addtitle><description>Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.</description><subject>Disease</subject><subject>Environmental factors</subject><subject>Gene deletion</subject><subject>Genetic analysis</subject><subject>Genetic diversity</subject><subject>Genetics</subject><subject>Genotype &amp; phenotype</subject><subject>Intellectual disabilities</subject><subject>KCNQ3 protein</subject><subject>Parents &amp; parenting</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Potassium channels (voltage-gated)</subject><subject>Proteins</subject><subject>Siblings</subject><subject>Ubiquitin-protein ligase</subject><issn>1434-5161</issn><issn>1435-232X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkUtLxDAUhYMoPkZ_gBsJuHFTvUmaNl2K-ALBzQjuQpomTsa2qUmrzL8344wuXJ174NyPyz0InRK4JMDEVSSQJAMKGQioMrGDDknOeEYZfd39mfOMk4IcoKMYl5DStKT76IAxYCWr4BC9zxcGu8b0o7NOq9H5HnuLxy-PBzUu_JvpncafKjjVjxG7HitsVefaFf5y4wKnqcGqb3A0nyYYbH3o4prQJN_6oUtk1SbXqtUx2rOqjeZkqzP0cnc7v3nInp7vH2-unzLNgI-ZgZxTKkquhOW2sJY1uizAlIrUtAbKQHNVasF4XRMNda3qptBU5FbzyubAZuhiwx2C_5hMHGXnojZtq3rjpyhpnlcVLxlnKXr-L7r0U-jTdZJyyAsqeLkGkk1KBx9jMFYOwXUqrCQBuW5CbpqQqQm5bkKKtHO2JU91Z5q_jd_Xs2_Tk4R8</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Miyake, Noriko</creator><creator>Heydari, Shermineh</creator><creator>Garshasbi, Masoud</creator><creator>Saitoh, Shinji</creator><creator>Nasiri, Jafar</creator><creator>Hamanaka, Kohei</creator><creator>Takata, Atsushi</creator><creator>Matsumoto, Naomichi</creator><creator>Beheshti, Farnaz Hosseini</creator><creator>Chaleshtori, Ahmad Reza Salehi</creator><general>Nature Publishing Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6911-3351</orcidid></search><sort><creationdate>20210401</creationdate><title>The identification of two pathogenic variants in a family with mild and severe forms of developmental delay</title><author>Miyake, Noriko ; Heydari, Shermineh ; Garshasbi, Masoud ; Saitoh, Shinji ; Nasiri, Jafar ; Hamanaka, Kohei ; Takata, Atsushi ; Matsumoto, Naomichi ; Beheshti, Farnaz Hosseini ; Chaleshtori, Ahmad Reza Salehi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c305t-e04522875a8f5f6ff3dc760e7a1b2b0230c5a7c835bb1c0bbabd6c284fc59f403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Disease</topic><topic>Environmental factors</topic><topic>Gene deletion</topic><topic>Genetic analysis</topic><topic>Genetic diversity</topic><topic>Genetics</topic><topic>Genotype &amp; phenotype</topic><topic>Intellectual disabilities</topic><topic>KCNQ3 protein</topic><topic>Parents &amp; parenting</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Potassium channels (voltage-gated)</topic><topic>Proteins</topic><topic>Siblings</topic><topic>Ubiquitin-protein ligase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyake, Noriko</creatorcontrib><creatorcontrib>Heydari, Shermineh</creatorcontrib><creatorcontrib>Garshasbi, Masoud</creatorcontrib><creatorcontrib>Saitoh, Shinji</creatorcontrib><creatorcontrib>Nasiri, Jafar</creatorcontrib><creatorcontrib>Hamanaka, Kohei</creatorcontrib><creatorcontrib>Takata, Atsushi</creatorcontrib><creatorcontrib>Matsumoto, Naomichi</creatorcontrib><creatorcontrib>Beheshti, Farnaz Hosseini</creatorcontrib><creatorcontrib>Chaleshtori, Ahmad Reza Salehi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyake, Noriko</au><au>Heydari, Shermineh</au><au>Garshasbi, Masoud</au><au>Saitoh, Shinji</au><au>Nasiri, Jafar</au><au>Hamanaka, Kohei</au><au>Takata, Atsushi</au><au>Matsumoto, Naomichi</au><au>Beheshti, Farnaz Hosseini</au><au>Chaleshtori, Ahmad Reza Salehi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The identification of two pathogenic variants in a family with mild and severe forms of developmental delay</atitle><jtitle>Journal of human genetics</jtitle><addtitle>J Hum Genet</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>66</volume><issue>4</issue><spage>445</spage><epage>448</epage><pages>445-448</pages><issn>1434-5161</issn><eissn>1435-232X</eissn><abstract>Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>33037390</pmid><doi>10.1038/s10038-020-0809-8</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0001-6911-3351</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1434-5161
ispartof Journal of human genetics, 2021-04, Vol.66 (4), p.445-448
issn 1434-5161
1435-232X
language eng
recordid cdi_proquest_miscellaneous_2449957353
source Alma/SFX Local Collection
subjects Disease
Environmental factors
Gene deletion
Genetic analysis
Genetic diversity
Genetics
Genotype & phenotype
Intellectual disabilities
KCNQ3 protein
Parents & parenting
Patients
Phenotypes
Potassium channels (voltage-gated)
Proteins
Siblings
Ubiquitin-protein ligase
title The identification of two pathogenic variants in a family with mild and severe forms of developmental delay
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T01%3A31%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20identification%20of%20two%20pathogenic%20variants%20in%20a%20family%20with%20mild%20and%20severe%20forms%20of%20developmental%20delay&rft.jtitle=Journal%20of%20human%20genetics&rft.au=Miyake,%20Noriko&rft.date=2021-04-01&rft.volume=66&rft.issue=4&rft.spage=445&rft.epage=448&rft.pages=445-448&rft.issn=1434-5161&rft.eissn=1435-232X&rft_id=info:doi/10.1038/s10038-020-0809-8&rft_dat=%3Cproquest_cross%3E2449957353%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2504628570&rft_id=info:pmid/33037390&rfr_iscdi=true