Table 5.

Clinical Impact of Genetic Testing in Kidney Diseases

Indication	Genetic Finding	Genetic Diagnosis	Clinical Impact	References
Steroid-resistant nephrotic syndrome	Homozygous Fin-major mutation in NPHS1	Nephrotic syndrome type 1 (OMIM #256300)	Increased risk of posttransplant disease recurrence	57, 58
	COQ2 mutation	CoQ10 deficiency 1 (OMIM #607426)	CoQ10 supplementation can attenuate proteinuria and extrarenal complications such as encephalopathy	59, 60
	COL4A3 or COL4A4 missense mutation	Alport syndrome (OMIM #104200; #203780) or TBMD (OMIM #141200)	•Distinguishes between autosomal (COL4A3 or COL4A4) and X-linked (COL4A5) inheritance, informing family counseling •Missense mutations are associated with less severe disease and slower progression to kidney failure and loss-of-function mutations •Avoids immunosuppression (a commonly used therapy for nephrotic syndrome)	61-64
Cystic renal dysplasia	17q12 deletion	Renal cysts and diabetes syndrome (OMIM #137920)	Multisystem work-up for associated extrarenal complications, including testing for diabetes, exocrine pancreatic insufficiency, hepatic function, neurologic anomalies, and/or neurocognitive impairment	65-67
Nephrolithiasis	APRT mutation	APRT deficiency (OMIM #614723)	Xanthine dehydrogenase inhibition to prevent crystalline nephropathy and allograft loss	68, 69
Episodic hypertension	SDHD mutation	Hereditary paraganglioma-pheochromocytoma syndrome (OMIM #168000)	•Imaging studies to screen for additional tumors •Catecholamine antagonists and/or surgical tumor resection •Knowledge of parent-of-origin effect due to maternal imprinting informs genetic counseling •Lower risk of malignancy than other genetic causes of familial paraganglioma-pheochromocytoma syndromes informs prognosis	70, 71
Failure to thrive, hepatomegaly, and hyperuricemia	G6PC mutation	Glycogen storage disease Ia (OMIM #232200)	•Dietary therapy (frequent meals, nasogastric tube, and/or raw starch to prevent hypoglycemia; oral bicarbonate and avoidance of fructose and glucose to prevent acidosis) •Surveillance for hepatic adenoma; liver transplant may be needed	72, 73

Note: Reproduced from Groopman et al⁵⁶ with permission of Springer Nature.

Abbreviations: APRT, adenine phosphoribosyltransferase; COL4A, collagen type IV α-chain; CoQ₁₀, coenzyme Q₁₀; COQ2, coenzyme Q2, polyprenyltransferase; G6PC, glucose-6-phosphatase catalytic subunit; NPHS1, nephrin; SDHD, succinate dehydrogenase complex subunit D; TBMD, thin basement membrane disease.