Primary ciliary dyskinesia in Egypt: First report of cilia ultrastructural defects and novel genetic variants

Abstract Background Primary ciliary dyskinesia (PCD) is a genetic disorder that follows several inheritance patterns predominately autosomal recessive. It is caused by aberrant motile cilia structure and/or function. Diagnosis of PCD is challenging, involving complex technical steps and requiring special expertise. Here, we report the first attempt to employ transmission electron microscopy (TEM) to precisely diagnose PCD in Egypt. The study aims to outline the findings of diagnostic procedures, including TEM and genetic analysis, carried out on a cohort of Egyptian patients clinically suspected of having PCD. Methods A cohort of 48 individuals underwent testing to determine their PCD status. The diagnostic modalities used included genetic and TEM analysis. Clinical features and diagnostic test outcomes were described. Results PCD was confirmed in 27 of the 48 participating cases. Class 1 hallmark defects were the most commonly detected TEM findings. Outer dynein arm defect in addition to microtubular disorganization with inner dynein arm loss was found equally to be the most common diagnostic defects in the confirmed cases. A highly heterogeneous genetic background was found with 14 different affected genes. Of these, CCDC39 was the most commonly mutated one. The variants, c.430‐1G>A in DNAAF6 , c.8099C>T in DNAH11 , c.263T>C in DNAL1 , c.1154dup in NEK10 , c.487C>T in HYDIN , and c.90+1G>C in CCDC39 gene were detected novel variants. Conclusion Diagnosis of PCD is challenging especially in low‐ and middle‐income countries. As there is no single reference diagnostic test, integrating diagnostic modalities, such as TEM and genetics, can enhance diagnosis.