RT Journal Article
SR Electronic
T1 The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00714-2022
DO 10.1183/23120541.00714-2022
VO 9
IS 2
A1 Nisreen Rumman
A1 Mahmoud R. Fassad
A1 Corine Driessens
A1 Patricia Goggin
A1 Nader Abdelrahman
A1 Adel Adwan
A1 Mutaz Albakri
A1 Jagrati Chopra
A1 Regan Doherty
A1 Bishara Fashho
A1 Grace M. Freke
A1 Abdallah Hasaballah
A1 Claire L. Jackson
A1 Mai A. Mohamed
A1 Reda Abu Nema
A1 Mitali P. Patel
A1 Reuben J. Pengelly
A1 Ahmad Qaaqour
A1 Bruna Rubbo
A1 N. Simon Thomas
A1 James Thompson
A1 Woolf T. Walker
A1 Gabrielle Wheway
A1 Hannah M. Mitchison
A1 Jane S. Lucas
YR 2023
UL http://openres.ersjournals.com/content/9/2/00714-2022.abstract
AB 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 (FEV1) 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 (FEV1 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.Despite limited resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD cohorts globally. There is notable familial homozygosity within the context of significant population heterogeneity. https://bit.ly/3HTo96x