Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder.
Details
Serval ID
serval:BIB_CB1B9259E590
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder.
Journal
Genetics in medicine
ISSN
1530-0366 (Electronic)
ISSN-L
1098-3600
Publication state
Published
Issued date
07/2021
Peer-reviewed
Oui
Volume
23
Number
7
Pages
1246-1254
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
To elucidate the novel molecular cause in families with a new autosomal recessive neurodevelopmental disorder.
A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization.
Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons.
Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder.
A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization.
Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons.
Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder.
Keywords
Humans, Intellectual Disability/genetics, Neurodevelopmental Disorders/genetics, Pedigree, Exome Sequencing
Pubmed
Web of science
Open Access
Yes
Create date
12/04/2021 12:10
Last modification date
22/02/2023 1:15