Abstract: PUB177
Preliminary Results of Genotyping of ADPKD in the Multiethnic Population of South Africa
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Mbobnda, Cedric Kapche, University of KwaZulu-Natal College of Health Sciences, Durban, KZN, South Africa
- Assounga, Alain Guy Honoré, University of KwaZulu-Natal College of Health Sciences, Durban, KZN, South Africa
Background
Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent heritable kidney disorder. It is characterised by the progressive development of kidney cysts, leading to loss of kidney function and end-stage kidney failure (ESKD). It is primarily caused by the PKD1 and PKD2 genes, which account for 85% and 15 % of cases, respectively. Genotyping in African populations is scarce. This study aimed to investigate the genotype-phenotype relationship in a multiracial population in South Africa.
Methods
Six out of 40 patients with a clinical diagnosis of ADPKD followed up at the Inkosi Albert Luthuli Central were studied for the PKD1 gene using multiplex long-range PCR followed by next-generation sequencing on peripheral blood DNA. Briefly, the PKD1 gene was amplified and subsequently sequenced; amplicon reads were aligned to the PKD1 gene reference using minimap2, SAM tools and BCF tools for downstream analysis.
Results
Of the six participants, only one was male, and 3 were Black Africans, 2 White and 1 Indian/Asian. Absence of family history was noted in 2 black Africans. The Mean age at diagnosis and ESKD were 46.13 ±7.22 and 51.80±11.47, respectively. Hypertension and kidney failure were the most common complications, and liver cyst was the most frequent extra-renal manifestation (Table 1). Preliminary genotyping results of one Indian/Asian participant with early manifestations of CKD requiring dialysis by age 46, revealed PKD1 mutations including: 1 truncating nonsense mutation c.12420 G>A previously published and 1 new missense variant c.12417 G>A which significance is still to be established
Conclusion
These preliminary results may explain the rapidly progressive disease with ESKD by age 46. The analysis of the remaining genotypes is on-going
Clinical characteristics of participants
| CX001 | CX002 | CX004 | CX006 | CX008 | CX0011 | |||
| Age at diagnosis of ADPKD | 49 | 44 | 44 | 36 | 58 | 46 | ||
| Age at ESKD | 67 | N/A | 44 | 41 | 61 | 46 | ||
| Sex | Female | Female | Male | Female | Female | Female | ||
| Race/Ethnicity | White | White | Black African | Black African | Black African | Indian/Asian | ||
| Family History | Polycystic Kidney Disease | Yes | Yes | Yes | No | No | Yes | |
| ESKD | Yes | Yes | Yes | No | No | No | ||
| Comorbid conditions | None | None | HIV | HIV | Hepatitis B | None | ||
| Clinical manifestations | HTN | HTN | HTN | HTN, Heamaturia | HTN | HTN | ||
| ADPKD Complications | Abdominal wall hernia, liver cyst | liver cyst | None | None | Liver cyst | Liver cyst | ||
Funding
- Government Support – Non-U.S.