Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00076003" target="_blank" >RIV/65269705:_____/22:00076003 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/22:10434450 RIV/00216208:11130/22:10434450 RIV/00216224:14310/22:00125072

Výsledek na webu

<a href="https://www.nature.com/articles/s10038-021-00988-w" target="_blank" >https://www.nature.com/articles/s10038-021-00988-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s10038-021-00988-w" target="_blank" >10.1038/s10038-021-00988-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development

Popis výsledku v původním jazyce

Pathogenic sequence variant in the GNAI1 gene were recently introduced as a cause of novel syndrome with a manifestation of variable developmental delay and autistic features. In our study, we report a case of monozygotic twins with severe intellectual disability and motor delay and developmental dysphasia. Both probands and their parents were examined using multi-step molecular diagnostic algorithm including whole-exome sequencing (WES), resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815 A&gt;G, p.(Asp272Gly) in probands. Using WES we also verified the microarray findings of a familial 8q24.23q24.3 duplication and heterozygous 5q13.2 deletion, not associated with clinical symptoms in probands. Our results confirmed the role of the GNAI1 gene in the pathogenesis of syndromic neurodevelopmental disorders. They support trio- or quatro-based WES as a suitable molecular diagnostics method for the simultaneous detection of clinically relevant sequence variants and CNVs in individuals with neurodevelopmental disorders and rare diseases.

Název v anglickém jazyce

Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development

Popis výsledku anglicky

Pathogenic sequence variant in the GNAI1 gene were recently introduced as a cause of novel syndrome with a manifestation of variable developmental delay and autistic features. In our study, we report a case of monozygotic twins with severe intellectual disability and motor delay and developmental dysphasia. Both probands and their parents were examined using multi-step molecular diagnostic algorithm including whole-exome sequencing (WES), resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815 A&gt;G, p.(Asp272Gly) in probands. Using WES we also verified the microarray findings of a familial 8q24.23q24.3 duplication and heterozygous 5q13.2 deletion, not associated with clinical symptoms in probands. Our results confirmed the role of the GNAI1 gene in the pathogenesis of syndromic neurodevelopmental disorders. They support trio- or quatro-based WES as a suitable molecular diagnostics method for the simultaneous detection of clinically relevant sequence variants and CNVs in individuals with neurodevelopmental disorders and rare diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

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

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Journal of Human Genetics

ISSN

1434-5161

e-ISSN

1435-232X

Svazek periodika

67

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

209-214

Kód UT WoS článku

000722168400001

EID výsledku v databázi Scopus

2-s2.0-85120803424