University of Oulu

Kankuri- Tammilehto, M.,Sauna- aho, O., & Arvio, M. (2021). Neurocognitive follow- up in adult siblings with Phelan– McDermidsyndrome due to a novel SHANK3 splicing sitemutation. Molecular Genetics & Genomic Medicine, 9, e1780.

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

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Author: Kankuri-Tammilehto, Minna1,2; Sauna-aho, Oili3; Arvio, Maria4,5
Organizations: 1Department of Clinical Genetics, Turku University Hospital, Turku, Finland
2Institute of Biomedicine, University of Turku, Turku, Finland
3KTO, Support and Expert Center for Persons with Intellectual Disability, Southwest Special Care Municipal Authority, Paimio, Finland
4Neurology, Päijät-Häme Joint Municipal Authority, Lahti, Finland
5PEDEGO, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2022-02-18


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.

Methods: 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.

Conclusions: 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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Series: Molecular genetics & genomic medicine
ISSN: 2324-9269
ISSN-E: 2324-9269
ISSN-L: 2324-9269
Volume: 9
Issue: 12
Article number: e1780
DOI: 10.1002/mgg3.1780
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3111 Biomedicine
Copyright information: © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.