Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD. The pathogenic potential of the variants was evaluated computationally and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.
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The authors would like to thank the patients and their families for their cooperation and interest in the study. We would also like to thank all the clinicians for patient referral. The technical assistance of the laboratory staff and Shikha Chandel is gratefully acknowledged. We are also thankful to Indian Council of Medical Research (ICMR), and Ganga Ram Institute of Postgraduate Medical Education and Research (GRIPMER), Sir Ganga Ram Hospital, New Delhi for providing financial aid.
The study was financially supported by Indian Council of Medical Research (ICMR), New Delhi vide sanction no. IRIS ID 2011-09610. Partial financial support was also provided by Ganga Ram Institute of Postgraduate Medical Education and Research (GRIPMER) (RDB project no: 4.9.14).
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Pandita, S., Ramachandran, V., Balakrishnan, P. et al. Identification of PKD1 and PKD2 gene variants in a cohort of 125 Asian Indian patients of ADPKD. J Hum Genet 64, 409–419 (2019). https://doi.org/10.1038/s10038-019-0582-8
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