Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 26, 2024; 12(3): 503-516
Published online Jan 26, 2024. doi: 10.12998/wjcc.v12.i3.503
Genetic investigation of the ubiquitin-protein ligase E3A gene as putative target in Angelman syndrome
Wiem Manoubi, Marwa Mahdouani, Dorra Hmida, Ameni Kdissa, Aida Rouissi, Ilhem Turki, Neji Gueddiche, Najla Soyah, Ali Saad, Christian Bouwkamp, Ype Elgersma, Soumaya Mougou-Zerelli, Moez Gribaa
Wiem Manoubi, Marwa Mahdouani, Dorra Hmida, Ameni Kdissa, Ali Saad, Soumaya Mougou-Zerelli, Moez Gribaa, Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse 4000, Tunisia
Wiem Manoubi, Marwa Mahdouani, Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir 3000, Tunisia
Aida Rouissi, Ilhem Turki, Department of Neuropediatry, La Rabta Hospital, Tunis 2000, Tunisia
Neji Gueddiche, Department of Pediatric, Fattouma Bourguiba Hospital Monastir, Monastir 2003, Tunisia
Najla Soyah, Department of Pediatric, Farhat Hached University Hospital, Sousse 4000, Tunisia
Christian Bouwkamp, Ype Elgersma, Department of Neuroscience, Erasmus MC, the Netherlands, Rotterdam 3112 td, Netherlands
Author contributions: Manoubi W wrote the manuscript; Mahdouani M and Kdissa A revised the manuscript for scientific content; Hmida D, Rouissi A, Turki I, Gueddiche N, Soyah N and Mougou-Zerelli S diagnosed patients; Saad A, Bouwkamp C and Elgersma Y, designed the study and prepared of the manuscript; Gribaa M supervised and corrected the manuscript; All authors have read and approve the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Science and Research Office of Farhat Hached Hospital.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interests.
Data sharing statement: All the parents of the suspected Angelman syndrome patients, whose samples and data were used in our research, have signed consent to share their samples and data with the physician/research responsible for the study. The consent is provided in French and Arabic which are the official languages of our country.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wiem Manoubi, BSc, Research Scientist, Researcher, Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Street Ibn El Jazzar, Sousse 4000, Tunisia. wiem.manoubi@yahoo.fr
Received: October 31, 2023
Peer-review started: October 31, 2023
First decision: November 28, 2023
Revised: December 12, 2023
Accepted: January 4, 2024
Article in press: January 4, 2024
Published online: January 26, 2024
Processing time: 78 Days and 17.6 Hours
Core Tip

Core Tip: Angelman syndrome (AS) is caused by maternal chromosome 15q11q13 deletions, imprinting defects, paternal uniparental disomy 15, and ubiquitin-protein ligase E3A (UBE3A) gene mutations. UBE3A is a brain-specific imprinting gene that encodes a ubiquitin-protein ligase. Here, we describe the variants in the UBE3A coding region detected by sequencing analysis in 50 AS Tunisian individuals with a normal bi-parental inheritance and methylation pattern of 15q11q13. Seven polymorphisms were found in our patients, including three novel variants. To identify bi-allelic recessive mutations that give rise to AS-like phenotypes, we considered consanguineous families, as they are more likely to develop such a recessive disease.