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Low grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis like syndrome

Harvard Dataverse (Africa Rice Center, Bioversity International, CCAFS, CIAT, IFPRI, IRRI and WorldFish)

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Title Low grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis like syndrome
 
Identifier https://doi.org/10.7910/DVN/O46MPP
 
Creator Cogliati, Francesca
Bedeschi, Maria Francesca
Russo, SIlvia
 
Publisher Harvard Dataverse
 
Description This dataset contains the data for the paper 'Low grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis like syndrome Loss-of-function' by Cogliati et al. 2024.
Loss-of-function CHD2 (Chromodomain helicase DNA binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early-onset generalized seizures, photosensitivity and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families.
We detect the first case of parental gonosomal CHD2 mosaicism disclosed in two brothers showing mild ID, born to healthy parents. The eldest brother has a history of drug-controlled generalized tonic-clonic seizures and displays sleep disorder and aggressive behavior suggestive of Smith-Magenis Syndrome (SMS).
Analysis of brothers’ DNAs by NGS custom gene panel for pediatric epilepsy and/or ID disclosed in both the same pathogenic CHD2 variant. Additional NGS experiment on genomic DNA from parents’ peripheral blood and from buccal swab raised the suspicion of low-grade gonosomal mosaicism in the unaffected mother subsequently confirmed by digital-PCR.
This report underlines as worthwhile CHD2 screening in individuals presenting ID/developmental delay, with/without epilepsy, and behavior and sleep disorders suggestive of SMS. Detecting a CHD2 variant should prime testing probands’ parents by NGS coupled to digital-PCR on different tissues to exclude/confirm gonosomal mosaicism and define the recurrence risk.
 
Subject Medicine, Health and Life Sciences
 
Date 2024-02-23
 
Contributor Cogliati, Francesca