Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10412221" target="_blank" >RIV/00216208:11130/20:10412221 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/20:00115870 RIV/65269705:_____/20:00073211 RIV/00064203:_____/20:10412221

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kK9Qj_gaOK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kK9Qj_gaOK</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10048-020-00616-3" target="_blank" >10.1007/s10048-020-00616-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy

Popis výsledku v původním jazyce

Pathogenic sequence variants in the IQ motif- and Sec7 domain-containing protein 2 (IQSEC2) gene have been confirmed as causative in the aetiopathogenesis of neurodevelopmental disorders (intellectual disability, autism) and epilepsy. We report on a case of a family with three sons; two of them manifest delayed psychomotor development and epilepsy. Initially proband A was examined using a multistep molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, both with negative results. Therefore, probands A and B and their unaffected parents were enrolled for an analysis using targeted &quot;next-generation&quot; sequencing (NGS) with a gene panel ClearSeq Inherited Disease(XT)(Agilent Technologies) and verification analysis by Sanger sequencing. A novel frameshift variant in the X-linkedIQSEC2gene NM_001111125.2:c.1813_1814del, p.(Asp605Profs*3) on protein level, was identified in both affected probands and their asymptomatic mother, having skewed X chromosome inactivation (XCI) (100:0). As theIQSEC2gene is a known gene escaping from XCI in humans, we expect the existence of mechanisms maintaining the normal or enough level of the IQSEC2 protein in the asymptomatic mother. Further analyses may help to the characterization of the presented novel frameshift variant in theIQSEC2gene as well as to elucidate the mechanisms leading to the rare asymptomatic phenotypes in females.

Název v anglickém jazyce

Novel Familial IQSEC2 Pathogenic Sequence Variant Associated With Neurodevelopmental Disorders and Epilepsy

Popis výsledku anglicky

Pathogenic sequence variants in the IQ motif- and Sec7 domain-containing protein 2 (IQSEC2) gene have been confirmed as causative in the aetiopathogenesis of neurodevelopmental disorders (intellectual disability, autism) and epilepsy. We report on a case of a family with three sons; two of them manifest delayed psychomotor development and epilepsy. Initially proband A was examined using a multistep molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, both with negative results. Therefore, probands A and B and their unaffected parents were enrolled for an analysis using targeted &quot;next-generation&quot; sequencing (NGS) with a gene panel ClearSeq Inherited Disease(XT)(Agilent Technologies) and verification analysis by Sanger sequencing. A novel frameshift variant in the X-linkedIQSEC2gene NM_001111125.2:c.1813_1814del, p.(Asp605Profs*3) on protein level, was identified in both affected probands and their asymptomatic mother, having skewed X chromosome inactivation (XCI) (100:0). As theIQSEC2gene is a known gene escaping from XCI in humans, we expect the existence of mechanisms maintaining the normal or enough level of the IQSEC2 protein in the asymptomatic mother. Further analyses may help to the characterization of the presented novel frameshift variant in theIQSEC2gene as well as to elucidate the mechanisms leading to the rare asymptomatic phenotypes in females.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

<a href="/cs/project/NU20-07-00145" target="_blank" >NU20-07-00145: Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neurogenetics

ISSN

1364-6745

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

269-278

Kód UT WoS článku

000541406100001

EID výsledku v databázi Scopus

2-s2.0-85086770865