•	Providing the patient and family with the definitive cause of their disease
•	Placing the clinical phenotype into context by gene specific stratification and delivery of personalized medicine. This may have both immediate as well as future clinical implications. e.g. (1) it is increasingly recognized that heterozygous contiguous gene deletions in the 17q12 region (which includes the gene HNF1B) can result in congenital anomalies of the kidney and urinary tract (CAKUT) with a neurologic phenotype such as autism spectrum disorder or schizophrenia; (2) Future possible implications include allele specific drug treatments as it has been established for other genetic diseases like cystic fibrosis*
•	Allows precise genetic counseling for family planning. e.g. (1) prediction of disease recurrence; (2) providing the option for preimplantation genetic diagnosis.
•	Detection of previously unrecognized affected family members. e.g. (1) patients with dominantly inherited CAKUT can be asymptomatic in early disease stages. For instance, index patients with CAKUT secondary to PAX2 or GATA3 mutations may have affected parent/child or sibling with overlooked CAKUT which can only be detected by recognizing the genetic nature of the disease which can apparently present as “sporadic” case. This should trigger renal ultrasonographic screening for CAKUT in other family members; (2) identification of asymptomatic individuals harboring heterozygous COL4A4 or COL4A5 mutations, who should be monitored yearly for proteinuria and hypertension. Both of which may be the first sign of evolving chronic kidney disease.
•	Avoiding unnecessary diagnostic procedures, tests and treatments. e.g. (1) avoiding renal biopsy. For instance, in patients with congenital or infantile nephrotic syndrome who has established genetic diagnosis secondary to NPHS1 or NPHS2 mutations or for patients with characteristic nephronophthisis phenotype and NPHP1 mutations; (2) avoiding aggressive anti- recurrence treatment for FSGS in kidney transplant patients with FSGS secondary to NPHS2 mutations. The latter has been shown to have low recurrence risk; (3) patients with CAKUT secondary to HNF1B mutations may have elevated liver function tests. Acknowledging this as part of the HNF1B-mutation related phenotype can prevent unnecessary invasive investigation (such as liver biopsy for “idiopathic elevated LFTs”).
•	Early detection and treatment initiation of asymptomatic (or subtle) extra renal manifestations. e.g. (1) heterozygous mutations in HNF1B may cause “isolated CAKUT” or “syndromic CAKUT” that is associated with one or more of the following extra renal manifestations: maturity onset diabetes of the young (MODY type 5), hyperuricemia and hypomagnesaemia. Early identification of those conditions can lead to early monitoring and treatment; (2) similarly, deafness has been associated with three other CAKUT-causing mutations in EYA1, SALL1 or PAX2; (3) patients with CAKUT secondary to GATA3 mutations may have hypoparathyroidism which can be asymptomatic in early disease stages however should be recognized and treated.
•	Providing guidance for monitoring of potential future complications. e.g. (1) patients with nephrotic syndrome secondary to WT1 are at increased risk for WT1-related Wilms tumor; (2) patients with WT1 mutations in the donor splice site of intron-9, resulting in the splice form +KTS are at risk for gonadoblastoma; (3) patients with nephronophthisis secondary to NPHP5 mutations are at risk for progressive blindness secondary to retinitis pigmentosa (i.e. Senior-Løken syndrome)
•	Guiding advanced medical management on a gene specific basis. e.g. (1) recessive mutations in CTNS establish the diagnosis of cystinosis and should trigger treatment with cystine-depleting agents; (2) considering CoQ10 supplements for patients with nephrotic syndrome harboring mutations in genes of the CoQ10 biosynthesis pathway such as CoQ2, CoQ4 and ADCK4; (3) guiding thrombocytopenia management for patients with nephrotic syndrome secondary to MYH9 mutations.
* Lumacaftor and ivacaftor therapy have been specifically shown to have clinical efficacy in patients who are homozygous for the Phe508del CFTR mutation211.
“One author declares competing financial interests: F.H. receives royalties on a mutation analysis panel licensed to Claritas (Cambridge).”