Table 4:

Information on phenotype and histological diagnosis among families and family members, alteration to final diagnosis and potential alterations to treatment following next generation sequencing.

Family ID	No. of Affect ed Indivi duals	ID	Phenotype	Histological Diagnosis	Potential Change in Diagnosis	Genetic Diagnosis	Final Diagnosis (OMIM Phenotype MIM No.)	Material Change in Diagnosis	Potential Treatment Change	Nature of Change
2	4	2A	Progressive CKD, onset in 20s and early onset gout	TIKD or Gouty Nephropathy	Yes	UMOD	ADTKD–UMOD (603860)	No	No
		2B	Progressive CKD, onset in 20s and early onset gout	TI Fibrosis	Yes			No
		2C	Progressive CKD, onset in 20s and early onset gout	TI Fibrosis	Yes			No
		2D	Progressive CKD, onset in 20s and early onset gout	MPGN/ DDD	Yes			No
3	6	3A	Progressive non-proteinuric CKD, detected age 35	Familial TIKD	Yes	MUC1	ADTKD–MUC1 (174000)	No	No
		3B	Progressive non-proteinuric CKD detected age 38	Familial TIKD	Yes			No
		3C	Progressive non-proteinuric CKD detected mid-30s	Acute TI fibrosis	Yes			No
		3D	Progressive non-proteinuric CKD detected mid-30s	Familial TIKD	Yes			No
		3E	Progressive non-proteinuric CKD age 40	Familial TIKD	Yes			No
		3F	Progressive non-proteinuric CKD detected mid-30s	TI fibrosis	Yes			No
4	2	4A*	CKD mid-30s, diabetes mellitus & annulara pancreas	TIKD	Yes	HNF1B	ADTKD–HNF1B (137920)	No	Yes	Liver and parathyroid screening
		4B*	CKD age 42, diabetes mellitus	TMA	Yes			Yes
5	1	5A*	CKD, age 21, small cystic kidneys on renal US	TI Nephritis	Yes	NPHP1	Nephronophthisis 1, juvenile (256100)	No	No
6	2	6A*	Small cystic kidneys, retinitis pigmentosa, mild learning disability	Early Nephronophthisis	Yes	IFT140	Mainzer-Saldino Syndrome (266920)	No	No
		6B*	Small cystic kidneys, retinitis pigmentosa, mild learning disability	TMA & TIKD	Yes			No
7	1	7A	Low complement (C3), Gout, arthropathy, family history	Proliferative Glomerulonephritis	Yes	MUC1	ADTKD–MUC1 (174000)	Yes	Yes	Steroid avoidance
8	2	8A	Microscopic haematuria and CKD III	IgA Nephropathy	Yes	COL4A5	Alport syndrome I, X linked (301050)	Yes	Yes	ENT & Ophthalmology Review
		8B	Progressive CKD detected in 40s, haematuria detected in 20s	Arteriosclerosis with fibrosis	Yes			Yes
9	1	9A	Hypertension, proteinuria and haematuria	Focal proliferative GN	Yes	COL4A5	Alport syndrome I, X linked (301050)	Yes	Yes	ENT & Ophthalmology Review
11	1	11A	Progressive CKD, Glaucoma and hearing impairment	FSGS	Yes	COL4A5	Alport syndrome I, X linked (301050)	Yes	No
12	1	12A*	Haematuria and proteinuria, nephew with hearing loss	Alport Syndrome	No	COL4A5	Alport syndrome I, X linked (301050)	No	No
13	1	13A*	Progressive haematuria, CKD and hearing loss	Alport Syndrome	No	COL4A5	Alport syndrome I, X linked (301050)	No	No
14	1	14A*	Bilateral small kidneys, gout, retinitis pigmentosa, anaemia and pseudotumour cerebri	FSGS	Yes	FANCI	Fanconi Anaemia, complementation group I (609053)	Yes	Yes	Cancer screening
15	3	15A	Progressive CKD	TIKD	Yes	UMOD	ADTKD–UMOD (603860)	Yes	No
		15B	Progressive CKD in mid-50s, Bechet’s disease	Chronic TMA/FSGS	Yes			Yes
		15C	Sarcoidosis, CKD	Chronic TMA	Yes			Yes
16	1	16A	Haematuria, progressive CKD and hearing loss	Alport Syndrome	No	COL4A5	Alport syndrome I, X linked (301050)	No	No
17	1	17A	Haematuria, progressive CKD and hearing loss	Alport Syndrome	No	COL4A5	Alport syndrome I, X linked (301050)	No	No
18	4	18A	Progressive CKD, 1.8gm proteinuria, no evidence of systemic TMA	TMA & TBMN	Yes	INF2	Glomerulosclerosis, focal segmental, 5 (613237)	Yes	No
		18B	Proteinuria but normal renal function, age 42, no evidence of systemic TMA	TMA & TBMN	Yes			Yes
		18C	Proteinuria, progressive CKD, no evidence of systemic TMA	TMA & TBMN	Yes			Yes
		18D	Progressive CKD, ESRD age 36, no evidence of systemic TMA	TMA & TBMN	Yes			Yes
19	1	19A	Progressive CKD, no systemic evidence of TMA	TMA	Yes	MUC1	ADTKD–MUC1 (174000)	Yes	No
20	2	20A	Cystic kidney with slowly progressive CKD, raised liver enzymes, no evidence of systemic TMA	Acute TMA	Yes	HNF1B	ADTKD–HNF1B (137920)	Yes	Yes	Diabetic Screening
		20B	Congenital abnormality of the kidney	Oligomegonephronia	Yes			Yes
21	2	21A*	Low complement (C3) levels and normal renal function	Within normal limits	Yes	C3	C3 Deficiency (612925)	Yes	No
		21B*	ESKD age 23, bland urinalysis	Mesangial Proliferation	Yes	INF2	Glomerulosclerosis, focal segmental, 5 (613237)	Yes	No
22	1	22A*	CKD diagnosed aged 26, hypertension, father and sister with history of CKD	Arteriosclerosis	Yes	WNK4	Pseudo- hypoaldosteronism - hypertensive CKD (614491)	Yes	Yes	Salt avoidance and use of thiazides
23	1	23A*	Gout and progressive kidney disease and nephrotic range proteinuria in mid-20s	Severe fibrosis	Yes	SLC3A1	Cystinuria (220100)	Yes	Yes	Stone prevention, increased fluid intake

TMA, thrombotic microangiopathy; TBMN, thin basement membrane nephropathy; FSGS, Focal Segmental Glomerulosclerosis; TIKD, tubulointerstitial kidney disease; DDD, dense deposit disease

Genetic diagnosis as reported by Connaughton DM, Kennedy C, Shril S, et al. Monogenic causes of chronic kidney disease in adults. Kidney Int. February 2019. doi:10.1016/j.kint.2018.10.03