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Co-inheritance of pathogenic variants in PKD1 and PKD2 genes presenting as severe antenatal phenotype of autosomal dominant polycystic kidney disease.

Authors
  • Arora, Veronica1
  • Bijarnia-Mahay, Sunita2
  • Tiwari, Vaibhav3
  • Bansal, Savita4
  • Gupta, Pallav5
  • Setia, Nitika1
  • Puri, Ratna D1
  • Verma, Ishwar C1
  • 1 Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India. , (India)
  • 2 Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India. Electronic address: [email protected] , (India)
  • 3 Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, India. , (India)
  • 4 Department of Obstetrics and Gynaecology and Fetal Medicine, Fortis Escorts Hospital, Jaipur, Rajasthan, India. , (India)
  • 5 Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India. , (India)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Mar 01, 2020
Volume
63
Issue
3
Pages
103734–103734
Identifiers
DOI: 10.1016/j.ejmg.2019.103734
PMID: 31349084
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is caused by pathogenic variants in either PKD1 or PKD2 genes. Disease severity is dependent on various factors including the presence of modifier genes. We describe a family with recurrent foetal presentation of ADPKD due to co-inheritance of pathogenic variants in both PKD1 [c.3860T > C; p.(Leu1287Pro)] and PKD2 [(c.1000C > A; p.(Pro334Thr)] genes. Familial segregation studies revealed the mother and the father to be heterozygous for the same variants in the PKD1 and PKD2 genes, respectively, as found in the foetus. Renal ultrasonography detected evidence of cystic disease in the mother and two of her family members. No cysts were detected in the father, however the paternal grandfather died of renal cystic disease. The absence of disease in the father can be explained by the phenomenon of incomplete penetrance, or Knudson's two-hit hypothesis of cystogenesis in the grandfather. This case underscores the importance of sequencing PKD2 gene even in the presence of a familial PKD1 variant, as well as genetic testing of the cysts for evidence of the second hit. Copyright © 2019. Published by Elsevier Masson SAS.

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