Combining RSPH9 founder mutation screening and next-generation sequencing analysis is efficient for primary ciliary dyskinesia diagnosis in Saudi patients.

Autor: Mabrouk I; Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia. mabrouk_imed@yahoo.fr., Al-Harthi N; Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia., Mani R; Inserm UMR_S933, Sorbonne Université, Childhood Genetic Disorders, Hôpital Armand-Trousseau, Paris, France.; Unité de recherche UR14ES19, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia., Montantin G; U.F. de Génétique moléculaire (AP-HP), Sorbonne Université, Hôpital Armand-Trousseau, Paris, France., Tissier S; U.F. de Génétique moléculaire (AP-HP), Sorbonne Université, Hôpital Armand-Trousseau, Paris, France., Lagha R; Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia., Ben Abdallah F; Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia., Hassan MM; Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia., Alhomrani M; Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia., Gaber A; Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia., Alsanie WF; Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia., Ouali H; Respiratory Clinic, King Faisal Medical Complex, Taif, 26514-8245, Saudi Arabia., Jambi FA; Pediatric Department, Maternity and Children Hospital, Makkah, Saudi Arabia., Almaghamsi TM; King Faisal Specialist Hospital and Research Center, Jeddah, 23433, Saudi Arabia., Alqarni NA; King Faisal Specialist Hospital and Research Center, Jeddah, 23433, Saudi Arabia., Alfarsi NA; King Faisal Specialist Hospital and Research Center, Jeddah, 23433, Saudi Arabia., Kashgari K; Pediatric Department, Maternity and Children Hospital, Jeddah, 23324, Saudi Arabia., Al-Zahrani HJ; Pediatric Department, Maternity and Children Hospital, Jeddah, 23324, Saudi Arabia., Al-Shamary ZA; Pediatric Department, King Khalid Hospital, Hail, 5032-55421, Saudi Arabia., Al-Harbi A; Pediatric Department, Al Hada Armed Forces Hospital, Taif, Saudi Arabia., Amselem S; Inserm UMR_S933, Sorbonne Université, Childhood Genetic Disorders, Hôpital Armand-Trousseau, Paris, France.; U.F. de Génétique moléculaire (AP-HP), Sorbonne Université, Hôpital Armand-Trousseau, Paris, France., Escudier E; Inserm UMR_S933, Sorbonne Université, Childhood Genetic Disorders, Hôpital Armand-Trousseau, Paris, France.; U.F. de Génétique moléculaire (AP-HP), Sorbonne Université, Hôpital Armand-Trousseau, Paris, France., Legendre M; Inserm UMR_S933, Sorbonne Université, Childhood Genetic Disorders, Hôpital Armand-Trousseau, Paris, France.; U.F. de Génétique moléculaire (AP-HP), Sorbonne Université, Hôpital Armand-Trousseau, Paris, France.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2022 Jul; Vol. 67 (7), pp. 381-386. Date of Electronic Publication: 2022 Jan 20.
DOI: 10.1038/s10038-021-01006-9
Abstrakt: Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy. Dysfunction of motile respiratory and nodal cilia results in sinopulmonary symptoms associated with laterality defects (LD) found in half of the patients. The molecular basis of the disease is insufficiently investigated in patients originating from the Arabian Peninsula. In a group of 16 unrelated Saudi patients clinically suspected of PCD and among whom only 5 (31%) had LD, we first screened by PCR-RFLP two founder mutations, RSPH9 c.804_806del and CCDC39 c.2190del previously identified in patients from the Arabian Peninsula and Tunisia, respectively. When negative, targeted panel or whole-exome sequencing was performed. Three patients were homozygous for the mutation in RSPH9, which encodes an axonemal protein that is absent from nodal cilia. None of the patients carried the CCDC39 founder mutation frequent in Tunisia. NGS analysis showed that nine patients had homozygous mutations in PCD genes. In total, sequential RFLP and NGS analysis solved 75% (12/16) of cases and identified ten distinct mutations, among which six are novel, in nine different genes. These results, which highlight the genetic heterogeneity of PCD in Saudi Arabia, show that the RSPH9 c.804_806del mutation is a prevalent mutation among Saudi patients, whereas the CCDC39 c.2190del ancestral allele is most likely related to the Berber population. This study shows that RSPH9 founder mutation first-line screening and NGS analysis is efficient for the genetic exploration of PCD in Saudi patients. The RSPH9 founder mutation accounts for the low rate of LD among Saudi patients.
(© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
Databáze: MEDLINE
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