Screening of Angelman Syndrome deletion and methylation aberration using MS-MLPA assay in a Tunisian population

Abstract

Background: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, absent speech, dysmorphic facial features, microcephaly, epileptic seizures, Electroencephalography (EEG) abnormalities and neurological problem. Four known molecular mechanisms lead to a deficiency in maternal UBE3A expression and consequently to AS: (1) Deletion of the AS critical region on the maternal chromosome 15q11.2–q13 (70%), (2) paternal uniparental disomy (pUPD) (2-7%), (3) imprinting defects (3–5%), and (4) mutations in the maternal copy of UBE3A (10%). Materials and methods: Here, we report 11 Tunisian AS patients suspected on the basis of clinical features, behavior, EEG findings and confirmed by molecular analysis using FISH technique, microsatellites study and Methylation Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA). Results: The diagnosis was confirmed in these patients (7 males, 4 females) by detecting the presence of deletion of the critical AS region on chromosome 15 through the use of fluorescence in situ hybridization (FISH) technique in 10 patients, and confirmed by Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA). A microsatellite analysis detected only one patient with uniparental disomy. Conclusion: Deletion and methylation aberration screening by MS-MLPA assay is considered as a rapid and cost-effective method to confirm Angelman syndrome diagnosis contributing to an early interventional therapy and genetic counseling should be provided. *Correspondence to: Wiem Manoubi, Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia, Tel: +216 73 102 500; E-mail: wiem.manoubi@yahoo.fr