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

Year 2024, Volume: 11 Issue: 1, 40 - 46, 30.04.2024

Tuğba Karaman Mercan , Vildan Çiftçi , Aslı Toylu , Banu Nur , Özden Clark , Sibel Berker Karauzum

https://doi.org/10.47572/muskutd.1349887

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.

Keywords

Angelman Syndrome, Cytogenetics, Next-Generation Sequencing, Translocations, Uniparental Disomy

De novo Paternal Uniparental Dizomiyle Ortaya Çıkan de novo der(15q;15q) taşıyan Angelman Sendromlu Olgu

Abstract

Angelman sendromu (AS; OMIM 105830), tipik olarak maternal kromozom 15q11.2-q13 delesyonu, Ubiquitin-protein ligaz E3A (UBE3A) gen mutasyonları, paternal uniparental disomi (UPD), imprinting merkez mutasyonlarının neden olduğu konjenital bir nörogelişimsel bozukluktur. UPD taşıyan sporadik AS oranı %2-3 olarak bilinmektedir. AS hastalarının yaklaşık %2-3'ünde paternal UPD saptanmıştır. Birçok rapor, UPD ile ilişkili AS olgularının heterodizomik olduğunu ileri sürmüştür. Bu yazıda AS tanısı konulan dört yaşında bir hasta sunulmaktadır. Hastanın dilini dışarı çıkaran geniş bir ağzı, her iki parmağını esnetmesi, zeka geriliğiyle birlikte salyası akması, konuşamaması, uyku bölünmesi, kendine zarar verme davranışı gibi dismorfik özellikleri gözlenmiştir. Angelman sendromu olgularının tanısında elektroensefalogram (EEG) bulguları önemli olmakla birlikte olgumuzda spesifik EEG ve ayrıca manyetik rezonans görüntüleme bulguları saptanmamıştır. Olgumuzda konvansiyonel sitogenetik yöntemle başlayan tanı sürecinde yeni nesil dizileme yöntemi kullanılarak genetik analiz tamamlanmıştır. 15. kromozomda iki uzun kolun Robertson tipi translokasyonu saptanan hastanın karyotipi 45,XX,der(15;15)(q10;q10)dn olarak tanımlanmıştır. Haplotip analizi, vakanın taşıdığı de novo rob(15q;15q) translokasyonun paternal kökenli 15 numaralı kromozom olduğunu göstermiştir. Literatürde UPD'li AS olgularının klinik bulgularının mikrodelesyonlulara göre daha hafif olması nedeniyle 15. kromozomun UPD'sini taşıyan AS olgularının gözden kaçabileceğini düşündürmektedir. Bu nedenle, burada sunulan vaka, geleneksel sitogenetik tarafından belirlenen der(15;15) translokasyonlarında, bireyin UPD için değerlendirilmesi gerektiğini gösteren iyi bir örnektir.

Keywords

Angelman Sendromu, Sitogenetik, Translokasyonlar, Uniparental Dizomi, Yeni Nesil Dizileme

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