Angelman syndrome (AS) is a congenital neuro-developmental disorder typically occurring due to functional defects of the UBE3A gene caused by uniparental disomy (UPD), translocation or single gene mutation. UBE3A gene exhibits imprinting expression, and only maternal inherited alleles express functional UBE3A protein in the brain. The common method to diagnose AS is single nucleotide polymorphism array or methylation‑specific multiplex ligation‑dependent probe amplification (MS‑MLPA). In recent years, whole exome sequencing (WES) has been increasingly used in the genetic diagnosis of a variety of indications, exhibiting great advantages as a comprehensive and unbiased testing method. In the present study, the cases of two unrelated patients with Robertsonian‑like translocation in chromosome 15, namely 45,XX,der(15;15)(q10;q10) and 45,XY,der(15;15)(q10;q10), are reported. The first case was diagnosed with AS by WES and validated by Sanger sequencing. In contrast to 42.84% homozygous variants on all chromosomes, 92.69% homozygosity variants were observed on chromosome 15. A homozygous stretch identifier was applied and identified a homozygous region across the entire chromosome 15. Sanger sequencing was used to further determine the subtype and confirm that two homozygous variants on chromosome 15 with low allele frequency (<0.01) were derived only from the father and not from the mother, thereby indicating a paternal UPD case, classified as isodisomy. MS‑MLPA results of the other AS patient with the same karyotype indicated that he had a high possibility of paternal UPD at chromosome 15. Taken together, the current study suggested the potential application of WES in detecting and facilitating the diagnosis of UPD.