Background:
The prevalence of kidney disease (KD) due to genetically inherited conditions in Ireland is unknown. Studies have shown that KD aggregates within families, with family history acting as a surrogate marker for genetically inherited disease. In our pilot study, the Irish Kidney Gene Project (IKGP), I established a 34.2% prevalence of familial kidney disease (FKD) in a representative sample (n=1840) of the KD population in Ireland. Identification of monogenic disease genes in families with KD has provided a strong basis for understanding disease mechanisms that will facilitate precise molecular diagnosis.
Aims:
1. Phenotype families with KD that demonstrate a high prevalence within the Irish cohort
2. Genotype these families to identify the underlying molecular defects causing KD
Methods:
The initial focus will be analysis of the IKGP cohort with integration of these data into the Rare Kidney Disease (RKD) Registry and Biobank at Trinity College Dublin, creating a subgroup of patients: the Irish Familial Kidney Disease Registry. I will obtain biological samples for DNA and perform phenotyping of familial clusters of KD. Using these Irish samples and pedigree data, I will undertake genetic analysis of Irish families who demonstrate familial clustering at the Renal Genetic Laboratory, Harvard Medical School. I plan to focus specifically on two disease entities; Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) and Nephronopthisis-Related Ciliopathies (NPHP-RC).
Anticipated Outcomes:
This study will be the first to provide information on the epidemiology of FKD in Ireland. Additionally, it will provide data on the aetiological determinants and phenotypic variants of FKD. It will allow for identification and definite diagnosis of those with FKD, which potentially can offer new insights into the pathogenesis of the disease. This research will provide key information for developing management strategies for patients with FKD in Ireland.