Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation

Abstract Background Phelan–McDermid syndrome (PMD) is usually not only caused by 22q13.3 deletion but also pathogenic variants (mutations) of SHANK3 gene. PMD is characterized by global intellectual disability, severely delayed or absent speech, and features of autism spectrum disorder and susceptib...

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Main Authors: Minna Kankuri‐Tammilehto, Oili Sauna‐aho, Maria Arvio
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Molecular Genetics & Genomic Medicine
Subjects:
Online Access:https://doi.org/10.1002/mgg3.1780
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author Minna Kankuri‐Tammilehto
Oili Sauna‐aho
Maria Arvio
author_facet Minna Kankuri‐Tammilehto
Oili Sauna‐aho
Maria Arvio
author_sort Minna Kankuri‐Tammilehto
collection DOAJ
description Abstract Background Phelan–McDermid syndrome (PMD) is usually not only caused by 22q13.3 deletion but also pathogenic variants (mutations) of SHANK3 gene. PMD is characterized by global intellectual disability, severely delayed or absent speech, and features of autism spectrum disorder and susceptibility to psychotic behavior. Here, we describe a neurocognitive follow‐up and genetic etiology for two siblings with PMD. Method Comparative genomic hybridization (CGH) array test was normal and no 22q13.3 deletion was observed. For this reason, whole exome sequencing (WES) analyzed the siblings’ and the parents’ DNA sample. Results The results of the siblings strongly suggest that the SHANK3 gene variant c.2313+1G>A is pathogenic and PMD can be inherited from a mosaic father for this gene variant. Both siblings learned new skills until puberty but experienced a neuropsychiatric disaster after the age of 14 years experienced neurocognitive decline and it was sharp for one of the siblings. Conclusion The long‐term observations are sparse in PMD and SHANK3 mutations. This is the neurocognitive follow‐up from childhood to middle ages, where a sharp neurocognitive decline was observed. We conclude that progressive neuropsychiatric symptoms in adolescence are a universal clinical clue for PMD diagnosis and an underlying SHANK3 splicing site mutation.
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spelling doaj.art-622024943e5f4ca08ceda7b30ed60b6e2022-12-21T18:46:13ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-12-01912n/an/a10.1002/mgg3.1780Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutationMinna Kankuri‐Tammilehto0Oili Sauna‐aho1Maria Arvio2Department of Clinical Genetics Turku University Hospital Turku FinlandKTO, Support and Expert Center for Persons with Intellectual Disability Southwest Special Care Municipal Authority Paimio FinlandNeurology Päijät‐Häme Joint Municipal Authority Lahti FinlandAbstract Background Phelan–McDermid syndrome (PMD) is usually not only caused by 22q13.3 deletion but also pathogenic variants (mutations) of SHANK3 gene. PMD is characterized by global intellectual disability, severely delayed or absent speech, and features of autism spectrum disorder and susceptibility to psychotic behavior. Here, we describe a neurocognitive follow‐up and genetic etiology for two siblings with PMD. Method Comparative genomic hybridization (CGH) array test was normal and no 22q13.3 deletion was observed. For this reason, whole exome sequencing (WES) analyzed the siblings’ and the parents’ DNA sample. Results The results of the siblings strongly suggest that the SHANK3 gene variant c.2313+1G>A is pathogenic and PMD can be inherited from a mosaic father for this gene variant. Both siblings learned new skills until puberty but experienced a neuropsychiatric disaster after the age of 14 years experienced neurocognitive decline and it was sharp for one of the siblings. Conclusion The long‐term observations are sparse in PMD and SHANK3 mutations. This is the neurocognitive follow‐up from childhood to middle ages, where a sharp neurocognitive decline was observed. We conclude that progressive neuropsychiatric symptoms in adolescence are a universal clinical clue for PMD diagnosis and an underlying SHANK3 splicing site mutation.https://doi.org/10.1002/mgg3.1780infantile autismintellectual disabilitymosaicismPhelan–McDermid syndromeSHANK3 splicing site mutation
spellingShingle Minna Kankuri‐Tammilehto
Oili Sauna‐aho
Maria Arvio
Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation
Molecular Genetics & Genomic Medicine
infantile autism
intellectual disability
mosaicism
Phelan–McDermid syndrome
SHANK3 splicing site mutation
title Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation
title_full Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation
title_fullStr Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation
title_full_unstemmed Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation
title_short Neurocognitive follow‐up in adult siblings with Phelan–McDermid syndrome due to a novel SHANK3 splicing site mutation
title_sort neurocognitive follow up in adult siblings with phelan mcdermid syndrome due to a novel shank3 splicing site mutation
topic infantile autism
intellectual disability
mosaicism
Phelan–McDermid syndrome
SHANK3 splicing site mutation
url https://doi.org/10.1002/mgg3.1780
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