Abstract: FR-PO332
A Novel PKD1 Variant Demonstrates a Disease-Modifying Role in Trans with a Truncating PKD1 Mutation in Patients with ADPKD
Session Information
- Cystic Kidney Diseases - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Genetic Diseases of the Kidney
- 801 Cystic Kidney Diseases
Author
- Ayoub, Medhat N., Ministry of Health- Mubarak Hospital, KUWAIT, Kuwait
Background
Phenotypes associated with ADPKD in the terms of age of onset of end stage renal disease (ESRD), associated liver disease and other extrarenal manifestations showed high level of variability between patients. This phenotypic variability can be attributed to genic and allelic heterogeneity. Another element that adds to the complexity of phenotypic variability in ADPKD is the involvement of modifier genes which is suggested by the intrafamilial phenotypic variability observed in ADPKD families.
Methods
Patients were clinically evaluated using ultrasound and RFT. PKD1 was genotyped using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries. The significance of missense variants was assessed using the ADPKD Mutation Database, multisequence alignments and substitution assessment tools.
Results
In our case, we propose that the novel variant (p.H1769Y) aggravated the disease phenotype in patients resulting in early onset of ESRD and renal enlargement.
Conclusion
In summary, clinical evaluation of patients along with genetic prediction tools suggest that the novel PKD1 variant has a disease-modifying role, rather than disease causing role, in trans with the truncating PKD1 mutation in the studied family.
Pedigree of the ADPKD family showing the PKD1 genotype of each member along with age and onset of ESRD.
Ultra soound of patients with the PKD1 novel variant and mutation.