Genomics in the Kidney Clinic Translation, Implementation and - PowerPoint PPT Presentation

Genomics in the Kidney Clinic Translation, Implementation and Challenges Dr Andrew Mallett Nephrologist, RBWH & MNHHS National Director, KidGen AGHA Renal Genetics Flagship

Why Kidneys? Frequency, Outcomes and the Nephron 1 in 8 Australian Adults have a marker of Kidney Disease Genetic or Inheritable Kidney Disease 1 in 10 Adults >250 Implicated genes, multiple disease spectra with renal disease 1 in 2 Children with renal disease Understanding remains significantly incomplete

Mission Statement The KidGen Collaborative is an Australian-based consortium of clinicians , genetic counsellors and researchers focused on providing a definitive diagnosis to patients with inherited forms of kidney disease within a multidisciplinary clinic. Goal Within a three year period standard care for patients with inherited kidney disease will include access to a multi-disciplinary clinic , with genomic testing and genetic counselling for the family where appropriate Aims 1. Provide equitable access to genomic technology within clinical care for Australian families with kidney disease. 2. Evaluate whether multidisciplinary clinics which include a nephrologist, clinical geneticist and genetic counsellor improve the outcome, patient experience and standard of care for patients with inherited kidney disease and their families 3. Expand knowledge of the causes of inherited kidney disease through gene validation and disease modelling. 4. Improve understanding of inherited kidney disease in the hope of developing new treatments .

Where are we? Nationwide – clinical, diagnostic, translational, research

What do we do? Bed to Bench … and back again

What do we do? Bed to Bench … and back again Gene Negative Family GBM Disorders Research Genomics Project Project Clinic & Diagnostic Genomic Evaluation Functional Genomics Nephrotic Syndrome Project Project Project Diagnostic Genomics Education & Outreach C3GN HiDDEn Services Initiatives Project Project

Progress Clinic & Diagnostic Genomic Evaluation AGHA Flagship - Evaluating Renal Genetics MDT Clinics Project

Progress Clinic & Diagnostic Genomic Evaluation AGHA Flagship - Evaluating Renal Genetics MDT Clinics Project

Progress LOST - L anguage and O ther S ocio-economic barriers to LOST Project T ranslation of genomic medicine to the clinic

Progress FOUND FOUND - FO llowing U p N ew renal genetic D iagnoses Project

Progress Diagnostic Genomics Reporting Genetic Diagnostic Outcomes Services N = 135 families 10 panels, 207 genes 43% Secured Genetic Dx (Pathogenic Variant/s) Mallett et al (2017), In Press

Progress Family Research Genomics Identifying Rare & Novel Genetic Causes Project 49 Families Proposed and Accepted for Recruitment o 4 Gene Negative Alport Syndrome/TBMN Sub Study • 32 Families Sequenced & Analyzed o 13 via WES o 28 via WGS o 1 via WES & WGS • 12 have a candidate variant/s in a known gene o 6 genes are very rare (<10 reported families)  3 genes were reported <24months prior  1 genes was reported within 6months • Reanalysis ongoing o New analysis elements being incorporated o 6 th monthly re-review “Mutations in mitochondrial DNA causing TIKD” Connor et al (2017)

Progress Functional Genomics Modelling Disease & Validating Variants Project disease modelling

Progress HIDDEN Flagship - w H ole genome I nvestigation to HIDDEN Flagship i D entify un DE tected N ephropathies

Progress HIDDEN Flagship - w H ole genome I nvestigation to HIDDEN Flagship i D entify un DE tected N ephropathies

Progress HIDDEN Flagship - w H ole genome I nvestigation to HIDDEN Flagship i D entify un DE tected N ephropathies New Patients and Change Australia Change from previous year 400 2500 200 2000 1500 0 1000 -200 500 0 -400 1985 1990 1995 2000 2005 2010 2015 New patients Change from previous year

Progress Education & Outreach An Annual National Event Initiatives

Intersections Collaborating with others Program 1 Patient & Consumer Program 2 Groups External Program 3 Partners Program 4

Where to from here? Progress through collaboration, evidence and understanding …… .. and realism KIDNEYS

Where to from here? Progress through collaboration, evidence and understanding …… .. and realism Goal Within a three year period standard care for patients with inherited kidney disease will include access to a multi-disciplinary clinic , with genomic testing and genetic counselling for the family where appropriate

Genomics in the Kidney Clinic Translation, Implementation and Challenges Dr Andrew Mallett Nephrologist, RBWH & MNHHS National Director, KidGen AGHA Renal Genetics Flagship