Genetic landscape and clinical outcomes of autosomal recessive polycystic kidney disease in Kuwait
Mariam E. Alhaddad,
Anwar Mohammad,
Khadija M. Dashti,
Sumi Elsa John,
Yousif Bahbahani,
Mohamed Abu-Farha,
Jehad Abubaker,
Thangavel Alphonse Thanaraj,
Laila Bastaki,
Fahd Al-Mulla,
Mohammad Al-Ali,
Hamad Ali
Affiliations
Mariam E. Alhaddad
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait
Anwar Mohammad
Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute (DDI), Dasman, Kuwait
Khadija M. Dashti
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait
Sumi Elsa John
Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait
Yousif Bahbahani
Division of Nephrology, Mubarak Al-Kabeer Hospital, Ministry of Health, Jabriya, Kuwait
Mohamed Abu-Farha
Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait
Jehad Abubaker
Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait
Thangavel Alphonse Thanaraj
Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait
Laila Bastaki
Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait
Fahd Al-Mulla
Department of Genetics and Bioinformatics, Dasman Diabetes Institute (DDI), Dasman, Kuwait
Mohammad Al-Ali
Next Generation Sequencing Laboratory, Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait
Hamad Ali
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; Corresponding author. Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Jabriya, Kuwait.
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.
