ZTTK syndrome: Clinical and molecular findings of 15 cases and a review of the literature.


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:
12 2021
Historique:
revised: 21 05 2021
received: 01 03 2021
accepted: 09 07 2021
pubmed: 1 8 2021
medline: 3 3 2022
entrez: 31 7 2021
Statut: ppublish

Résumé

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is caused by de novo loss-of-function variants in the SON gene (MIM #617140). This multisystemic disorder is characterized by intellectual disability, seizures, abnormal brain imaging, variable dysmorphic features, and various congenital anomalies. The wide application and increasing accessibility of whole exome sequencing (WES) has helped to identify new cases of ZTTK syndrome over the last few years. To date, there have been approximately 45 cases reported in the literature. Here, we describe 15 additional individuals with variants in the SON gene, including those with missense variants bringing the total number of known cases to 60. We have reviewed the clinical and molecular data of these new cases and all previously reported cases to further delineate the most common as well as emerging clinical findings related to this syndrome. Furthermore, we aim to delineate any genotype-phenotype correlations specifically for a recurring pathogenic four base pair deletion (c.5753_5756del) along with discussing the impact of missense variants seen in the SON gene.

Identifiants

pubmed: 34331327
doi: 10.1002/ajmg.a.62445
pmc: PMC8595531
mid: NIHMS1727740
doi:

Substances chimiques

DNA-Binding Proteins 0
Minor Histocompatibility Antigens 0
SON protein, human 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

3740-3753

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom

Informations de copyright

© 2021 Wiley Periodicals LLC.

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Auteurs

Sulagna Tina Kushary (ST)

Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, New York, USA.

Anya Revah-Politi (A)

Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, New York, USA.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Subit Barua (S)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Mythily Ganapathi (M)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Andrea Accogli (A)

IRCCS 'G. Gaslini' Children's Hospital, Genoa, Italy.

Vimla Aggarwal (V)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Nicola Brunetti-Pierri (N)

Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Department of Translational Medicine, Federico II University of Naples, Naples, Italy.

Gerarda Cappuccio (G)

Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Department of Translational Medicine, Federico II University of Naples, Naples, Italy.

Valeria Capra (V)

IRCCS 'G. Gaslini' Children's Hospital, Genoa, Italy.

Christina R Fagerberg (CR)

Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

Gabriella Gazdagh (G)

West of Scotland Centre for Genomic Medicine, Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, UK.

Edwin Guzman (E)

Division of Clinical Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.

Medard Hadonou (M)

St. George's Genomics Service, St. George's University Hospitals NHS FT, London, UK.

Victoria Harrison (V)

Wessex Clinical Genetics Service, Southampton, UK.

Kathrine Havelund (K)

HC Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

Daniela Iancu (D)

Wessex Clinical Genetics Service, Southampton, UK.

Alison Kraus (A)

Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

Natalie C Lippa (NC)

Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, New York, USA.

Mahesh Mansukhani (M)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Danielle McBrian (D)

Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.

Meriel McEntagart (M)

Department of Medical Genetics, St. George's University Hospital NHS FT, London, UK.

Marta Pacio-Míguez (M)

Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.

María Palomares-Bralo (M)

Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.

Carrie Pottinger (C)

Department of Clinical Genetics, All Wales Genomic Medicine Service, Maelor Hospital, Wrexham, UK.

Claudia A L Ruivenkamp (CAL)

Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Oliviero Sacco (O)

IRCCS 'G. Gaslini' Children's Hospital, Genoa, Italy.

Gijs W E Santen (GWE)

Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Fernando Santos-Simarro (F)

Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.

Marcello Scala (M)

IRCCS 'G. Gaslini' Children's Hospital, Genoa, Italy.

John Short (J)

St. George's Genomics Service, St. George's University Hospitals NHS FT, London, UK.

Kristina P Sørensen (KP)

HC Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

Christopher G Woods (CG)

Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Wellcome Trust Sanger Institute, Cambridge, UK.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.

Kwame Anyane Yeboa (K)

Division of Clinical Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.

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Classifications MeSH