Genetic landscape and clinical outcomes of autosomal recessive polycystic kidney disease in Kuwait.

Autor:	Alhaddad ME; Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait., Mohammad A; Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait., Dashti KM; Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait., John SE; Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait., Bahbahani Y; Division of Nephrology, Mubarak Al-Kabeer Hospital, Ministry of Health, Jabriya, Kuwait., Abu-Farha M; Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Abubaker J; Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Thanaraj TA; Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait., Bastaki L; Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Al-Mulla F; Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait., Al-Ali M; Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Ali H; Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait.; Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Jun 29; Vol. 10 (13), pp. e33898. Date of Electronic Publication: 2024 Jun 29 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e33898
Abstrakt:	Background: Autosomal recessive polycystic kidney disease (ARPKD), a rare genetic disorder characterized by kidney cysts, shows complex clinical and genetic heterogeneity. This study aimed to explore the genetic landscape of ARPKD in Kuwait and examine the intricate relationship between its genes and clinical presentation to enhance our understanding and contribute towards more efficient management strategies for ARPKD. Methods: This study recruited 60 individuals with suspected ARPKD from 44 different families in Kuwait. The participants were of different ethnicities and aged 0-70 years. Additionally, 33 were male, 15 were female, and 12 had indeterminant sex due to congenital anomalies. Comprehensive clinical data were collected. Mutations were identified by next-generation whole exome sequencing and confirmed using Sanger sequencing. Results: Of the 60 suspected ARPKD cases, 20 (33.3 %) died within hours of birth or by the end of the first month of life and one (1.7 %) within 12 months of birth. The remaining 39 (65.0 %) cases were alive, at the time of the study, and exhibited diverse clinical features related to ARPKD, including systematic hypertension (5.0 %), pulmonary hypoplasia (11.7 %), dysmorphic features (40.0 %), cardiac problems (8.3 %), cystic liver (5.0 %), Potter syndrome (13.3 %), developmental delay (8.3 %), and enlarged cystic kidneys (100 %). Twelve mutations, including novel truncating mutations, were identified in 31/60 cases (51.7 %) from 17/44 families (38.6 %). Additionally, 8/12 (66.7 %) mutations were in the PKHD1 gene, with the remaining four in different genes: NPHP3 , VPS13P , CC2D2A , and ZNF423 . Conclusions: This study highlights the spectrum of clinical features and genetic mutations of patients with ARPKD in Kuwait. It highlights the necessity for personalized approaches to improve ARPKD diagnosis and treatment, offering crucial insights into managing ARPKD. Competing Interests: The authors declare that they have no conflicts of interest regarding this study. (© 2024 The Authors.)
Databáze:	MEDLINE
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