Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review.


Journal

American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741

Informations de publication

Date de publication:
06 2021
Historique:
revised: 22 02 2021
received: 25 08 2020
accepted: 22 02 2021
pubmed: 7 3 2021
medline: 2 9 2021
entrez: 6 3 2021
Statut: ppublish

Résumé

De novo variants in the WDR26 gene leading to haploinsufficiency have recently been associated with Skraban-Deardorff syndrome. This condition is an ultra-rare autosomal dominant neurodevelopmental disorder characterized by a broad range of clinical signs, including intellectual disability (ID), developmental delay (DD), seizures, abnormal facial features, feeding difficulties, and minor skeletal anomalies. Currently, 18 cases have been reported in the literature and for only 15 of them a clinical description is available. Here, we describe a child with Skraban-Deardorff syndrome associated with the WDR26 pathogenic de novo variant NM_025160.6:c.69dupC, p.(Gly24ArgfsTer48), and an adult associated with the pathogenic de novo variant c.1076G > A, p.(Trp359Ter). The adult patient was a 29-year-old female with detailed information on clinical history and pharmacological treatments since birth, providing an opportunity to map disease progression and patient management. By comparing our cases with published reports of Skraban-Deardorff syndrome, we provide a genetic and clinical summary of this ultrarare condition, describe the clinical management from childhood to adult age, and further expand on the clinical phenotype.

Identifiants

pubmed: 33675273
doi: 10.1002/ajmg.a.62157
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
WDR26 protein, human 0

Types de publication

Case Reports Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1712-1720

Subventions

Organisme : NIMH NIH HHS
ID : MH111661
Pays : United States

Informations de copyright

© 2021 Wiley Periodicals LLC.

Références

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Auteurs

Lisa Pavinato (L)

Department of Medical Sciences, University of Turin, Turin, Italy.
Institute of Human Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.

Slavica Trajkova (S)

Department of Medical Sciences, University of Turin, Turin, Italy.

Enrico Grosso (E)

Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy.

Elisa Giorgio (E)

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Alessandro Bruselles (A)

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

Francesca Clementina Radio (FC)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Tommaso Pippucci (T)

Medical Genetics Unit, Polyclinic Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

Paola Dimartino (P)

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Marco Tartaglia (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Aleksandar Petlichkovski (A)

Institute for Immunobiology and Human Genetics, Faculty of Medicine, University "Sv. Kiril I Metodij", Skopje, Macedonia.

Silvia De Rubeis (S)

Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Joseph Buxbaum (J)

Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Giovanni Battista Ferrero (GB)

Department of Clinical and Biological Sciences, School of Medicine, University of Turin, Orbassano, Torino, Italy.

Roberto Keller (R)

Adult autism center, Mental Health Department, Local Health Unit ASL Città di Torino, Turin, Italy.

Alfredo Brusco (A)

Department of Medical Sciences, University of Turin, Turin, Italy.
Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy.

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