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

BACKGROUND

Angelman syndrome (AS) is caused by maternal chromosomal deletions, imprinting defects, paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase gene mutations. However the genetic basis remains unclear for several patients.

AIM

To investigate the involvement of 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 gene was screened for mutation detection. Two unrelated patients issued from consanguineous families were subjected to exome analysis.

RESULTS

We describe seven 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 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.