Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10429830" target="_blank" >RIV/00216208:11110/21:10429830 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/21:10429830

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-021-00886-z" target="_blank" >10.1038/s41588-021-00886-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

Popis výsledku v původním jazyce

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system.

Název v anglickém jazyce

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

Popis výsledku anglicky

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Nature Genetics

ISSN

1061-4036

e-ISSN

—

Svazek periodika

53

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

33

Strana od-do

1006-1038

Kód UT WoS článku

000668827300003

EID výsledku v databázi Scopus

2-s2.0-85111456769