Genomik imprinting bozukluklarda klinik bulgular ve genetik tanı

Pelin Ercoşkun; Serdar Bozlak; Alper Gezdirici; Mustafa Doğan; Aydeniz Aydın Gümüş; Lale Yilmaz Celik; Aynur İslamova; Tuna Eren Esen

doi:10.19161/etd.1637605

EN TR

Clinical features and genetic diagnosis of genomic imprinting disorders

Abstract

Aim: Genomic imprinting disorders are a group of disorders caused by a parental imprinting mechanism that disappears with various genetic alterations. The most common of these disorders are Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome and Silver-Russell syndrome. The aim of this study was to comprehensively analyze the clinical manifestations and genetic outcomes of patients with genomic imprinting disorders. Materials and Methods: Our study included 28 patients diagnosed with imprinting disorder between 2021 and 2024. DNA was isolated from peripheral blood samples obtained from the patients and methylation-specific MLPA was performed. Results: In the present study, 28 patients were included for analysis. Thirteen patients were diagnosed with Prader-Willi syndrome (PWS), eight with Angelman syndrome, three with Beckwith-Wiedemann syndrome, and four with Silver-Russell syndrome. The results of genetic tests were analyzed, revealing a deletion in the chromosome 15q11 region in six of the 13 patients with PWS and a PWS-specific methylation pattern in seven of them. In the cohort of patients diagnosed with Angelman syndrome, seven cases were found to have a deletion in the chromosome 15q11 region, while one patient exhibited an Angelman syndrome-specific methylation pattern. H19 hypomethylation was identified in all patients with Silver-Russell syndrome, and H19 hypermethylation and KCNQ1OT1 hypomethylation were observed in all patients with Beckwith-Wiedemann syndrome. An evaluation of the clinical findings of the patients revealed the presence of selective IgA deficiency, retinal dystrophy, and hearing loss in patients with Prader-Willi syndrome, which has not been previously reported. Furthermore, the prevalence of congenital cardiac anomalies and sleep apnea was found to be higher in this patient group compared to the literature. Conclusion: The intricate epigenetic mechanisms underlying genomic imprinting disorders, the variability in patient presentations, and the subtlety of the findings contribute to the complexity of the diagnostic process. We believe that our study will contribute to the literature in terms of rare clinical manifestations and genetic consequences of imprinting disorders.

Keywords

Genomik imprinting bozukluklarda klinik bulgular ve genetik tanı

Öz

Amaç: Genomik imprinting bozukluklar, çeşitli genetik değişikliklerle birlikte ortadan kalkan ebeveyne özgü baskılama mekanizmasının neden olduğu hastalıklar grubudur. Bu hastalıklar arasında en sık Prader-Willi sendromu, Angelman sendromu, Beckwith-Wiedemann sendromu ve Silver-Russell sendromu yer almaktadır. Bu çalışmanın amacı, genomik imprinting bozukluklarda meydana gelen klinik bulguları ve hastaların genetik sonuçlarını kapsamlı bir şekilde incelemektir. Gereç ve Yöntem: Çalışmamıza 2021-2024 yılları arasında imprinting bozukluk tanısı almış 28 hasta dahil edildi. Hastalardan alınan periferik kan örneklerinden DNA izolasyonu yapılarak metilasyon spesifik MLPA çalışması gerçekleştirildi. Bulgular: Çalışmamıza dahil edilen 28 hastanın 13’ü Prader-Willi sendromu (PWS), sekizi Angelman sendromu, üçü Beckwith-Wiedemann sendromu, dördü ise Silver-Russell sendromu tanısı almıştı. Genetik tetkik sonuçları incelendiğinde, PWS tanılı 13 hastanın altısında kromozom 15q11 bölgesinde delesyon yedisinde ise PWS spesifik metilasyon paterni tespit edildi. Angelman sendromlu hastaların yedisinde kromozom 15q11 bölgesinde delesyon, bir hastada ise Angelman sendromu spesifik metilasyon paterni izlendi. Silver-Russell sendromlu hastaların tamamında H19 hipometilasyonu, Beckwith-Wiedemann sendromlu hastaların tamamında ise H19 hipermetilasyonu ve KCNQ1OT1 hipometilasyonu saptandı. Hastaların klinik bulgularını değerlendirdiğimizde ise Prader-Willi sendromlu hastalarda daha önce bildirilmeyen selektif IgA eksikliği, retinal distrofi ve işitme kaybı bulgularını gözlemledik. Ayrıca PWS grubunda konjenital kardiyak anomali ve uyku apnesi sıklığı literatüre göre daha fazlaydı. Sonuç: Genomik imprinting bozuklukların altında yatan karmaşık epigenetik mekanizmalar, hastalar arasındaki fenotipik değişkenlikler ve silik bulgular hastalığın tanısını zorlaştırmaktadır. Çalışmamızın imprinting bozuklukların nadir görülen klinik bulguları ve genetik sonuçları açısından literatüre katkı sağlayacağını düşünmekteyiz.

Anahtar Kelimeler

Ethical Statement

Çalışmamız Başakşehir Çam ve Sakura Şehir Hastanesi etik kurulu onayını almıştır.

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Details

Primary Language

Turkish

Subjects

Medical Genetics (Excl. Cancer Genetics)

Journal Section

Research Article

Authors

Pelin Ercoşkun ^*
0000-0001-7791-0115
Türkiye

Serdar Bozlak
0000-0001-7275-431X
Türkiye

Alper Gezdirici
0000-0002-2432-9279
Türkiye

Mustafa Doğan
0000-0003-0464-6565
Türkiye

Aydeniz Aydın Gümüş
0000-0002-5879-6385
Türkiye

Lale Yilmaz Celik
0000-0002-9924-9206
Türkiye

Aynur İslamova
0009-0001-9757-3715
Türkiye

Tuna Eren Esen
0000-0001-8714-4768
Türkiye

Publication Date

March 9, 2026

Submission Date

February 11, 2025

Acceptance Date

November 4, 2025

Published in Issue

Year 2026 Volume: 65 Number: 1

DOI

https://doi.org/10.19161/etd.1637605

IZ

https://izlik.org/JA83WP88EN

Cite

RIS / Bibtex

Vancouver

1.Pelin Ercoşkun, Serdar Bozlak, Alper Gezdirici, Mustafa Doğan, Aydeniz Aydın Gümüş, Lale Yilmaz Celik, Aynur İslamova, Tuna Eren Esen. Genomik imprinting bozukluklarda klinik bulgular ve genetik tanı. EJM. 2026 Mar. 1;65(1):82-90. doi:10.19161/etd.1637605