Klinik Olarak Örtüşen Prader-Willi ve Prader-Willi Benzeri Sendromları’nın MS-MLPA ve aCGH ile değerlendirilmesi

Öz

ÖZ Amaç: Prader-Willi Sendromu (PWS), 15q11-q13 bölgesindeki paternal delesyonlar, maternal uniparental disomi (matUPD) ve gen mutasyonları ile ilişkili multisistemik bir hastalıktır. Prader-Willi Benzeri Sendrom (PWLS) olarak sınıflandırılan bazı olgular, 15q11-q13 bölgesinde değişiklik olmamasına rağmen PWS’ye benzer klinik özellikler gösterir. 1, 2, 6, 10, 12, 14 ve X kromozomlarındaki genetik değişikliklerin PWLS ile ilişkili olduğu öne sürülmekte olup, bu durum tanıyı zorlaştırmaktadır. Bu çalışmada PWS ile PWLS’nin ayrımını gösterebilmek için kriterlere uygun on bir olgunun metilasyon profillerinin belirlenmesi ve tüm kromozomlardaki olası değişimlerin tespiti amaçlanmıştır. Gereç ve Yöntemler: PWS fenotipine ve sitogenetik olarak normal karyotipe sahip, 15q11.2-q13 delesyonu bulunmayan on bir olgu çalışmaya dahil edilmiştir. Metilasyon-Spesifik-Multipleks-Ligasyon-Prob-Amplifikasyonu (MS-MLPA) ile bu bölgenin metilasyon analizi yapılmıştır. Normal metilasyon gösteren olgularda Array-Karşılaştırmalı-Genomik-Hibridizasyon (aCGH) ile genomdaki tüm bölgelerin kopya sayısı değişiklikleri incelenmiştir. Bulgular: On olgunun yalnız birinde anormal metilasyon paterni tespit edilmiştir. Dokuz olguda ise 15q11.2-q13 bölgesinde değişim gözlenmediğinden, bu olgular PWLS olarak değerlendirilmiştir. aCGH analizine dayanarak, PWLS (Prader Willi-benzeri sendrom) patogenezinde önemli olabilecek bazı değişiklikler tespit ettik. Sonuç: Yalnızca bir olguda PWS tespit edilmiş, diğer olgular ise PWLS kapsamında değerlendirilmiştir. PWLS grubunda aCGH ile, sendromun patogenezinde yer alabilecek bazı değişiklikler tespit edilmiştir. Ancak, klinik olarak anlamlı bir yorum yapılabilmesi ve PWLS etyolojisinin daha iyi anlaşılabilmesi için, tüm PWLS hastalarının ebeveynlerinin de aCGH ile incelenmesi gerekmektedir.

Anahtar Kelimeler

• PWS
• PWLS
• MS-MLPA
• aCGH
• 6q16.1-q21
• 15q11.2-q13
• UPD

Evaluation of Clinically Overlapping Prader-Willi and Prader-Willi-Like Syndromes Using MS-MLPA and aCGH

Abstract

Objective: Prader-Willi Syndrome (PWS) is a multisystemic disorder associated with paternal deletions, maternal uniparental disomy (matUPD), and mutations in the 15q11-q13 region. Prader-Willi-Like Syndrome (PWLS) cases, although lacking alterations in this region, display similar clinical features. Genetic variations in chromosomes 1, 2, 6, 10, 12, 14 and X have been suggested to contribute to PWLS, complicating diagnosis. This study aimed to analyze methylation profiles and identify possible genetic variations in all chromosomes to differentiate PWS from PWLS. Material and Methods: Eleven cases with PWS phenotypes normal cytogenetic karyotypes, and no 15q11.2-q13 deletions were included. Methylation-Specific-Multiplex-Ligation-Dependent-Probe-Amplification (MS-MLPA) was used for methylation analysis. In cases with normal methylation, Array Comparative Genomic Hybridization (aCGH) was used to evaluate entire regions of the genome for copy number variants. Results: An abnormal methylation pattern was detected in one case. The remaining nine cases showed no changes in the 15q11.2-q13 region and were classified as PWLS. Based on aCGH analysis of these patients, we found some alterations that might be important in PWLS pathogenesis. Conclusions: PWS was identified in only one case, while the others were classified as PWLS. Some alterations that can be involved in pathogenesis of PWLS were detected by aCGH in the PWLS group but to make a clinically significant interpretation and to better understand the etiology of PWLS, all PWLS patients’ parents have to be examined by aCGH too.

Keywords

• PWS
• PWLS
• MS-MLPA
• aCGH
• 6q16.1-q21
• 15q11.2-q13
• UPD

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