The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum.

Background: Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population.
Methods: Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV ₁ ) Global Lung Index z-scores and body mass index z-scores.
Results: 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes . CCDC39 , DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV ₁ z-score median -1.90 (-5.0-1.32)) and growth was mostly within the normal range (z-score mean -0.36 (-3.03-2.57). 19% individuals had finger clubbing.
Conclusions: Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity.
Competing Interests: Conflict of interest: N. Rumman received support for the present manuscript from two NIOX MINO devices from Circassia (previously called Aerocrine) to perform nasal nitric oxide testing and AAIR Charity funded whole-exome sequencing testing, and support for attending meetings and/or travel from the European Respiratory Society for a short term research training fellowship (3 months at Southampton University) (STRTF 2014-6816), outside the submitted work. M.R. Fassad received support for the present manuscript from a Wellcome Trust Collaborative Award in Science (210585/Z/18/Z). C. Driessens received support for the present manuscript from NHS England: work for this manuscript was performed while working for the National PCD Diagnostic Service at University Hospital Southampton; this service is commissioned and funded by NHS England. R. Pengelly received support for the present manuscript from Asthma Allergy and Inflammation Research. G. Wheway received support for the present manuscript from Asthma Allergy and Inflammation Research Trust; grants or contracts from UKRI COVID-19 Agile Response Fund, Wessex Medical Research/Rosetrees Trust PhD studentship, and Asthma Allergy and Inflammation Research Trust, outside the submitted work; stock or stock options for Illumina Inc., outside the submitted work; and receipt of equipment, materials, medical writing, gifts or other services from Synthego, outside the submitted work. H.M. Mitchison received support for the present manuscript from Great Ormond Street Children's Charity, NIHR Biomedical Research Centre at Great Ormond Street Hospital, and British Council Newton-Mosharafa Fund and Ministry of Higher Education in Egypt. J.S. Lucas received grants or contracts from NIHR, AAIR Charity, and NHS England, outside the submitted work. The remaining authors have nothing to disclose.
(Copyright ©The authors 2023.)