The Relationship between Genotype and Phenotype in Primary Ciliary Dyskinesia Patients

Objectives: Primary ciliary dyskinesia (PCD) is a chronic genetic disease that affects the respiratory tract, characterized by different clinical and laboratory features. It has a very difficult diagnosis, and high morbidity. In recent years, with the advances in genetics, the rate of diagnosis has increased considerably. In this study, it was aimed to evaluate the relationship between PCD patients' clinical, radiological and laboratory features and genetic analysis.
Methods: The study included 14 children who were diagnosed with PCD between 2015-2019 and underwent exome analysis. Diagnostic ages, body mass indexes (BMI)- Z score, clinical and radiological findings, pulmonary function tests, sputum culture reproduction and gene analysis were evaluated and compared.
Results: Six of the patients (43%) were girls and 8 (57%) were boys, and the median age at the time of diagnosis was 9 (min-max: 3-16) years. Genetic analysis revealed pathogenic mutations in DNAH5 (n=4, 29%), DNAH11 (n=2, 14%), RSPH4A (n=2, 14%), CCDC40 (n=2, 14%), DNAH9 (n=1, 7%), HYDIN (n=1, 7%), DNAH1 (n=1, 7%), and ARMC4 (n=1, 7%). Although not statistically significant, it was found that the diagnosis age was lower and the BMI Z-score was lower in CCDC40 mutations. Growth parametres were normal in DNAH5, DNAH11, RSPH4A and ARMC4 pathogenic variants. No significant correlation was found between genetic analysis and clinical features, culture reproduction and pulmonary function tests of the patients.
Conclusion: It is thought that more detailed information about the possible clinical features and prognosis of the disease can be obtained by genetic examinations of PCD. However, clinical trials with higher patient numbers are still needed.

Primer siliyer diskinezili hastalarýmýzda genotip-fenotip iliþkisi

Giriþ: Primer siliyer diskinezi (PSD), özellikle solunum yollarýný etkileyen, farklý klinik ve laboratuvar özellikleri ile karakterize kronik bir genetik hastalýktýr. Tanýsý oldukça zor olup, morbiditesi yüksektir. Son yýllarda genetik bilimindeki geliþmelerle birlikte hastalara taný koyulma oraný oldukça artmýþtýr. Bu çalýþmada, PSD hastalarýnýn klinik, radyolojik ve laboratuvar özellikleri ile genetik analizleri arasýndaki iliþkinin deðerlendirilmesi amaçlanmýþtýr.
Gereç ve yöntem: Çalýþmaya 2015-2019 tarihleri arasýnda PSD tanýsý konulan ve ekzom analizi yapýlan 14 çocuk dahil edildi. Hastalarýn taný yaþlarý, vücut kitle indeksleri (VKÝ)-Z skoru, klinik ve radyolojik bulgularý, solunum fonksiyon testleri, balgam kültür üremeleri ve gen analizleri incelendi ve kýyaslamasý yapýldý.
Bulgular: Hastalarýn 6’sý (% 43) kýz, 8’i (%57) erkek olup, taný anýndaki medyan yaþ deðeri 9 (min-maks: 3-16) yýldý. Genetik analizlerinde DNAH5 (n: 4, %29), DNAH11 (n: 2, %14), RSPH4A (n: 2, %14), CCDC40 (n: 2, %14), DNAH9 (n: 1, %7), HYDIN (n: 1, %7), DNAH1 (n: 1, %7), ARMC4 (n: 1, %7) patojenik mutasyonlarý saptandý. Ýstatistiksel olarak anlamlý olmasa da CCDC40 mutasyonlarýnda taný yaþýnýn daha küçük olduðu ve VKÝ Z- skorunun daha düþük olduðu tespit edildi. DNAH5, DNAH11, RSPH4A ve ARMC4 patojenik varyantlarýnda ise büyüme ve geliþme normal bulundu. Hastalarýn genetik analizleri ile klinik özellikleri, kültür üremeleri ve solunum fonksiyon testleri arasýnda anlamlý iliþki saptanmadý.
Sonuç: PSD hastalarýnýn genetik incelemeleri sonucu elde edilen verilerle hastalýðýn olasý klinik özellikleri ve prognozu hakkýnda daha detaylý bilgiler elde edilebileceði düþünülmektedir. Fakat yine de daha yüksek hasta sayýlý klinik araþtýrmalara ihtiyaç duyulmaktadýr. (SETB-2020-05-048)