A Case with Angelman Syndrome Carried de novo der(15q;15q) By de novo Paternal Uniparental Disomy

Abstract

Angelman syndrome (AS; OMIM 105830) is a congenital neurodevelopmental disorder typically caused by maternal chromosome 15q11.2-q13 deletion, Ubiquitin-protein ligase E3A (UBE3A) gene mutations, paternal uniparental disomy (UPD), or imprinting center mutations. The rate of sporadic Angelman syndrome carrying UPD is known to be 2-3%. Paternal UPD has been detected in approximately 2-3% of AS patients. Many reports have suggested that patients with UPD-associated AS cases are heterodisomic. We reported a case of a 4-year-old patient diagnosed with AS. She presented with dysmorphic features, including a wide mouth with protruding tongue, flexion of both fingers, drooling with mental retardation, absence of speech, disrupted sleep, without self-injuring behavior. Although electroencephalogram (EEG) findings are important to diagnosing AS, specific EEG and also magnetic resonance imaging (MRI) findings were not detected in our case. In the diagnostic process, which began with conventional cytogenetics, genetic analysis was completed using the next-generation sequencing method. A Robertsonian-type translocation of two long arms in derivative chromosome 15 was detected, defining the patient's karyotype as 45,XX,der(15;15)(q10;q10)dn. Haplotype analysis confirmed the presence of paternal uniparental disomy, indicating that the case carried a de novo rob(15q;15q) translocation. The literature, suggests that AS cases with UPD may exhibit milder clinical features compared to those with microdeletion. Consequently, AS cases involving UPD of chromosome 15 can sometimes be overlooked. Therefore, the case presented here serves as an example highlighting the need to evaluate individuals with translocations involving der(15;15) identified through conventional cytogenetics for potential UPD.