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

Nisreen Rumman; Mahmoud R Fassad; Corine Driessens; Patricia Goggin; Nader Abdelrahman; Adel Adwan; Mutaz Albakri; Jagrati Chopra; Regan Doherty; Bishara Fashho; Grace M Freke; Abdallah Hasaballah; Claire L Jackson; Mai A Mohamed; Reda Abu Nema; Mitali P Patel; Reuben J Pengelly; Ahmad Qaaqour; Bruna Rubbo; N Simon Thomas; James Thompson; Woolf T Walker; Gabrielle Wheway; Hannah M Mitchison; Jane S Lucas

doi:10.1183/23120541.00714-2022

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

ERJ Open Res. 2023 Apr 17;9(2):00714-2022. doi: 10.1183/23120541.00714-2022. eCollection 2023 Mar.

Authors

Nisreen Rumman^{1

2

3

4}, Mahmoud R Fassad^{5

6

4}, Corine Driessens^{7

8

9

4}, Patricia Goggin^{8

10

4}, Nader Abdelrahman¹¹, Adel Adwan³, Mutaz Albakri¹¹, Jagrati Chopra⁷, Regan Doherty^{8

10}, Bishara Fashho², Grace M Freke⁵, Abdallah Hasaballah¹², Claire L Jackson^{7

8}, Mai A Mohamed^{5

13}, Reda Abu Nema¹⁴, Mitali P Patel⁵, Reuben J Pengelly¹⁵, Ahmad Qaaqour¹¹, Bruna Rubbo^{7

8}, N Simon Thomas^{15

16}, James Thompson^{7

8

10}, Woolf T Walker^{7

8}, Gabrielle Wheway¹⁵, Hannah M Mitchison^{17

18}, Jane S Lucas^{7

8

18}

Affiliations

¹ Pediatric Department, Makassed Hospital, East Jerusalem, Palestine.
² Caritas Hospital, Bethlehem, Palestine.
³ Al-Quds University, School of Medicine, East Jerusalem, Palestine.
⁴ Joint first authors.
⁵ Genetics and Genomic Medicine Department, University College London, UCL Great Ormond Street Institute of Child Health, London, UK.
⁶ Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
⁷ Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK.
⁸ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁹ NIHR Applied Research Collaboration Wessex, University of Southampton, Southampton, UK.
¹⁰ Biomedical Imaging Unit, University of Southampton Faculty of Medicine, Southampton, UK.
¹¹ Internal Medicine Department, Makassed Hospital, East Jerusalem, Palestine.
¹² Rantisi Hospital, Gaza, Palestine.
¹³ Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University, Ash Sharqiyah, Egypt.
¹⁴ Al-Mustaqbal Medical Center, Hebron, Palestine.
¹⁵ Human Development and Health, University of Southampton Faculty of Medicine, Southampton, UK.
¹⁶ Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK.
¹⁷ Genetics and Genomic Medicine Research and Teaching Department, University College London, UCL Great Ormond Street Institute of Child Health, London, UK.
¹⁸ Joint senior authors.

Abstract

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.