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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome
American Journal of Human Genetics, Volume 110, No. 12, Year 2023
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Description
Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance in Man (OMIM) database. Through GeneMatcher, we identified ten individuals from eight families with a severe neurodevelopmental syndrome featuring variable manifestations. Clinical manifestations included hypotonia, global developmental delay, severe intellectual disability, brain abnormalities, musculoskeletal, and gastrointestinal abnormalities. Genetic analysis revealed five different homozygous loss-of-function variants in WBP4. Immunoblotting on fibroblasts from two affected individuals with different genetic variants demonstrated a complete loss of protein, and RNA sequencing analysis uncovered shared abnormal splicing patterns, including in genes associated with abnormalities of the nervous system, potentially underlying the phenotypes of the probands. We conclude that bi-allelic variants in WBP4 cause a developmental disorder with variable presentations, adding to the growing list of human spliceosomopathies. © 2023 American Society of Human Genetics
Authors & Co-Authors
Oja, Kaisa Teele
Estonia, Tartu
Tartu Ülikooli Kliinikum
Estonia, Tartu
Tartu Ülikool
Maroofian, Reza
United Kingdom, London
Ucl Queen Square Institute of Neurology
Guimier, Anne
France, Paris
Inserm
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Zaki, Maha S.
Egypt, Cairo
Human Genetics and Genome Research Institute
Gleeson, Joseph G.
United States, La Jolla
University of California, San Diego
Pajusalu, Sander
Estonia, Tartu
Tartu Ülikooli Kliinikum
Estonia, Tartu
Tartu Ülikool
Wojcik, Monica Hsiung
United States, Cambridge
Massachusetts Institute of Technology
Lee, Hane
South Korea, Seoul
3billion Inc.
Bauer, Peter
Germany, Rostock
Centogene ag
Zifarelli, Giovanni
Germany, Rostock
Centogene ag
Houlden, Henry H.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Elpeleg, Orly N.
Israel, Jerusalem
Hadassah University Medical Centre
Israel, Jerusalem
Hebrew University of Jerusalem
Amiel, Jeanne
France, Paris
Inserm
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Lyonnet, Stanislas L.
France, Paris
Inserm
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Gordon, Christopher T.
France, Paris
Inserm
Harel, Tamar
Israel, Jerusalem
Hadassah University Medical Centre
Israel, Jerusalem
Hebrew University of Jerusalem
Öunap, Katrin
Estonia, Tartu
Tartu Ülikooli Kliinikum
Estonia, Tartu
Tartu Ülikool
Mor-Shaked, Hagar
Israel, Jerusalem
Hadassah University Medical Centre
Israel, Jerusalem
Hebrew University of Jerusalem
Statistics
Citations: 2
Authors: 18
Affiliations: 14
Identifiers
Doi:
10.1016/j.ajhg.2023.10.013
ISSN:
00029297
Research Areas
Disability
Genetics And Genomics