Early-onset parkinsonism in PPP2R5D-related neurodevelopmental disorder

Hetzelt, Katalin L.M.L.; Kerling, Frank; Kraus, Cornelia; Rauch, Christophe; Thiel, Christian T.; Winterholler, Martin; Reis, André; Zweier, Christiane (2021). Early-onset parkinsonism in PPP2R5D-related neurodevelopmental disorder. European journal of medical genetics, 64(1), p. 104123. Elsevier 10.1016/j.ejmg.2020.104123

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PPP2R5D-related neurodevelopmental disorder (NDD) is a rare autosomal-dominant disease with developmental delay and mild to severe intellectual disability. So far, fewer than 30 affected individuals with mostly recurrent, de novo missense variants in PPP2R5D were reported. Recently, parkinsonism with an onset between 20 and 40 years was reported in four adult individuals with the same p.(Glu200Lys) variant in PPP2R5D. By trio exome sequencing we now identified the variant p.(Glu198Lys) in a 29 year old woman presenting with typical clinical manifestations of PPP2R5D-related neurodevelopmental disorder and additionally with motor decline and levodopa responsive, early-onset parkinsonism from her mid-twenties on. Accordingly, a clear reduction of dopamine transporter in the striatum on both sides was revealed by brain scintigraphy. Our findings further expand the molecular and clinical spectrum of PPP2R5D-related NDD and confirm the association with parkinsonism in early adulthood. This has marked implications for prognosis of PPP2R5D-related NDDs and for the therapeutic management of motor decline and parkinson-like symptoms in affected individuals.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinics of Human Genetics

UniBE Contributor:

Zweier, Christiane Gertrud

ISSN:

1878-0849

Publisher:

Elsevier

Language:

English

Submitter:

Christiane Zweier

Date Deposited:

14 Jan 2021 10:19

Last Modified:

18 Feb 2021 08:38

Publisher DOI:

10.1016/j.ejmg.2020.104123

PubMed ID:

33338668

BORIS DOI:

10.48350/150507

URI:

https://boris.unibe.ch/id/eprint/150507

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