What is Nephro Genetics?
Advancements in genetic diagnostic technology have revealed multiple variants in various genes involved in kidney pathophysiology. This has led to a deeper understanding of several renal disorders.
Prevalance Genetic Renal Disorders (GRD)
Studies indicate that renal disorders are not just environmental but also genetic, affecting 5-15% of the total adult population. In fact, 20% of CKD cases are thought to be due to genetic forms of renal disease, as proved by familial clustering and differing prevalence rates across ethnic groups1. The prevalence of renal diseases in children ranges from 21 to 55 per million age representative population. Countries with high rates of consanguinity and potentially greater risks of autosomal ESRD are reported to have hereditary renal diseases2.
-  Mallett A, Patel C, Salisbury A, et al. Orphanet Journal of Rare Diseases. 2014;9:98
-  Fletcher, J., McDonald, S., Alexander, S.I. et al. Pediatr Nephrol (2013) 28: 251
The cystic kidney diseases are also known as renal cystic ciliopathies. Some of these are:
- Autosomal Dominant/Recessive Polycystic kidney disease (ADPKD/ARPKD)
- Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)
Renal tubular function governs reabsorption of water and solutes from the glomerular filtrate. In renal tubulopathies the primary genetic defect causes loss of function of a specific renal transport protein or signalling molecule. The following are classified under genetic renal tubular disorders.
- Bartter syndrome
- Gitelman syndrome
- Pseudohypoaldosteronism (Type1/2)
Glomerulonephritis and glomerulosclerosis are the two major categories of glomerular diseases. Genetic glomerular diseases are:
- Steroid resistant nephrotic syndrome (SRNS)
- Familial Atypical hemolytic uremic syndrome (aHUS)
- Alport Syndrome
- Fibronectin glomerulopathy
The heritability of renal stone formation has long been recognized and the advent of the genomic era has greatly increased the potential to define its underlying genetic defects. These defects which lead to stone formation have been valuable in defining renal pathophysiology in these diseases.
- Primary Hyperoxaluria
- Hereditary Xanthinuria
- Dent disease
CAKUT accounts for approximately 50% of children with end-stage kidney disease. They occur in about 3 to 6 per 1,000 live births and constitute 20–30% of all anomalies identified in the neonatal period. CAKUT may present as an isolated feature or as part of clinical syndromes. Single-gene mutations in many different genes may cause a wide phenotypic spectrum of CAKUT and these are listed below.
- Renal agenesis
- Renal hypodysplasia
- Multicystic renal dysplasia
- Vesicoureteral reflux
Why test patients for Genetic Renal Disorders?
Highly penetrant mutations cause a wide range of renal phenotypes including:
- Diseases of renal growth (eg: polycystic kidney disease)
- Diseases of abnormal glomerular function (eg: congenital nephrotic syndrome)
- Abnormalities of blood pressure and electrolyte homeostasis (eg: Bartter syndrome)
Correct diagnosis of GRD impacts
- Leads to specific investigations
- Optimization of treatment regimens
- Socio-economic benefits to individual and family
Who needs to be tested for Genetic Renal Disorders?
- Individuals with the symptoms of a kidney disorder
- Individuals with a standard preliminary test showing the possibility of a kidney disorder
- Individuals with a positive family history of kidney disorder
- Individuals without a positive family history and if any individuals in the family with symptoms resembling a specific disease condition
- Prenatal testing is recommended only in families with a history of affected individuals
Why MedGenome Actia?
With an in-depth understanding of the disease and the latest research, Actia has developed a broad range of pre-designed gene mutation panels.
- Polycystic Kidney Disease Gene panel (ARPKD: PKHD1/ADPKD: PKD1 & PKD2)
- Meckel Gruber Syndrome gene panel
- VHL Gene analysis
- Von Hippel-Lindau Syndrome (VHL) deletion/duplication analysis
- Joubert Syndrome gene panel
- Bardet-Biedl Syndrome gene panel
- TSC1 & TSC2 gene analysis
- Bartter Syndrome gene panel
- Nephrotic Syndrome gene pane
- Hemolytic Uremic Syndrome - HUS (CFH, CFHR1 & CFHR3) deletion duplication analysis
- Primary Hyperoxaluria gene panel
- Homocystinuria gene panel
- Clinical exome