Paediatrics Publications

Title

Detection of a dna methylation signature for the intellectual developmental disorder, x-linked, syndromic, armfield type

Document Type

Article

Publication Date

2-1-2021

Journal

International Journal of Molecular Sciences

Volume

22

Issue

3

First Page

1

Last Page

13

URL with Digital Object Identifier

10.3390/ijms22031111

Abstract

A growing number of genetic neurodevelopmental disorders are known to be associated with unique genomic DNA methylation patterns, called episignatures, which are detectable in peripheral blood. The intellectual developmental disorder, X-linked, syndromic, Armfield type (MRXSA) is caused by missense variants in FAM50A. Functional studies revealed the pathogenesis to be a spliceosomopathy that is characterized by atypical mRNA processing during development. In this study, we assessed the peripheral blood specimens in a cohort of individuals with MRXSA and detected a unique and highly specific DNA methylation episignature associated with this disorder. We used this episignature to construct a support vector machine model capable of sensitive and specific identification of individuals with pathogenic variants in FAM50A. This study contributes to the expanding number of genetic neurodevelopmental disorders with defined DNA methylation episignatures, provides an additional understanding of the associated molecular mechanisms, and further enhances our ability to diagnose patients with rare disorders.

This document is currently not available here.

Share

COinS