Genetic investigation of the ubiquitin-protein ligase E3A gene as putative target in Angelman syndrome  

作　　者：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 

机构地区：[1]Laboratory of Human Cytogenetics,Molecular Genetics and Reproductive Biology,Farhat Hached University Hospital,Sousse 4000,Tunisia [2]Higher Institute of Biotechnology of Monastir,University of Monastir,Monastir 3000,Tunisia [3]Department of Neuropediatry,La Rabta Hospital,Tunis 2000,Tunisia [4]Department of Pediatric,Farhat Hached University Hospital,Sousse 4000,Tunisia [5]Department of Neuroscience,Erasmus MC,the Netherlands,Rotterdam 3112 td,Netherlands

出　　处：《World Journal of Clinical Cases》2024年第3期503-516,共14页世界临床病例杂志

摘　　要：BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.

关 键 词：Angelman syndrome Ubiquitin-protein ligase E3A EXOME CONSANGUINITY POLYMORPHISM 

分 类 号：R74[医药卫生—神经病学与精神病学]