Asset Details
Do you wish to reserve the book?
Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome
Do you wish to request the book?
Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome
2022
Overview
Autosomal recessive Cohen syndrome is a neurodevelopmental disorder characterized by postnatal microcephaly, intellectual disability, and a typical facial gestalt. Genetic variants in
VPS13B
have been found to cause Cohen syndrome, but have also been linked to autism, retinal disease, primary immunodeficiency, and short stature. While it is well established that loss-of-function mutations of
VPS13B
cause Cohen syndrome, the relevance of missense variants for the pathomechanism remains unexplained. Here, we investigate their pathogenic effect through a systematic re-evaluation of clinical patient information, comprehensive in silico predictions, and in vitro testing of previously published missense variants. In vitro analysis of 10 subcloned
VPS13B
missense variants resulted in full-length proteins after transient overexpression. 6/10 VPS13B missense variants show reduced accumulation at the Golgi complex in the steady state. The overexpression of these 6/10 VPS13B missense variants did not rescue the Golgi fragmentation after the RNAi-mediated depletion of endogenous
VPS13B
. These results thus validate 6/10 missense variants as likely pathogenic according to the classification of the American College of Medical Genetics through the integration of clinical, genetic, in silico
,
and experimental data. In summary, we state that exact variant classification should be the first step towards elucidating the pathomechanisms of genetically inherited neuronal diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Autism
/ Child
/ Developmental Disabilities - genetics
/ Developmental Disabilities - pathology
/ Disease
/ Genetics
/ Humanities and Social Sciences
/ Humans
/ Intellectual Disability - genetics
/ Intellectual Disability - pathology
/ Muscle Hypotonia - pathology
/ Mutation
/ Myopia
/ Neurodevelopmental disorders
/ Neurodevelopmental Disorders - genetics
/ Obesity
/ Proteins
/ Science
