Table 3. Clinical and genetic data of patients in the discovery cohort with disease-causing mutations in an SRNS/FSGS gene and patients with mutations in an SRNS/FSGS gene and COL4A3.

Patient	Gender	Familial/sporadic	Age at onset (years)	Features at presentation	Renal biopsy	Immunosuppressive therapy	Evolution	Gene	Mutation 1 (MG)	Mutation 2 (MG)	Gene	Mutation (MG)
Patients in the discovery cohort with disease-causing mutations in an SRNS/FSGS gene
319	M	Sp	0	CNS	NP	—	Dead at 1 year	NPHS1	c.468C>G	c.3478C>T
									p.(Y156*) (A)	p.(R1160*) (A)
336	M	Sp	0	CNS	CNF	—	ESRD at 2 months	NPHS1	c.1655C>A	c.1655C>A
									p.(A552D) (B)	p.(A552D) (B)
299	F	Sp	0.1	CNS	NP	—	ESRD at 8 months	NPHS1	c.3250dup	c.3250dup
									p.(V1084Gfs*12) (A)	p.(V1084Gfs*12) (A)
324	M	Sp	0.3	NS without edema	DMS	Cs, CP, CsA, MMF −	Normal Cr at 19 years	NPHS1	c.1930+5G>A	c.1930+5G>A
									p.(V634Tfs*13) (A)	p.(V634Tfs*13) (A)
363	F	Sp	0	CNS	NP	—	Cr 0.37 mg/dl at 1 month	NPHS2	c.413G>C	c.413G>A
									p.(R138P) (B)	p.(R138Q) (B)
330	F	Fama	0.2	Nephrotic proteinuria, MAL	DMS	—	Normal Cr at 4 months	NPHS2	c.320T>C	c.320T>C
									p.(L107P) (B)	p.(L107P) (B)
320	F	Sp	3	Denys–Drash syndrome	FSGS	—	ESRD at 4 years	WT1	c.1419T>A	—
									p.(H473Q) (B)
347-1	M	Famb	19	Non-nephrotic proteinuria	FSGS	—	CKD stage II at 20 years	INF2	c.658G>A	—
									p.(E220K) (B)
347-2	F	Famc	20	Nephrotic proteinuria	FSGS	Cs, CsA −	ESRD at 29 years	INF2	c.658G>A	—
									p.(E220K) (B)
384-1	F	Famb	27	Non-nephrotic proteinuria, MH, MAL	NP	—	Normal Cr at 32 years	TRPC6	c.2656G>A	—
									p.(E886K) (B)
384-2	M	Famd	30	MAL	NP	—	Normal Cr at 35 years	TRPC6	c.2656G>A	—
									p.(E886K) (B)
384-3	F	Famc	55	Non-nephrotic proteinuria, MH	NP	—	Normal Cr at 63 years	TRPC6	c.2656G>A	—
									p.(E886K) (B)
Patients with mutations in an SRNS/FSGS gene and COL4A3
266e	F	Sp	0	CNS, MH	NP	—	ESRD at 1 year	NPHS1f	c.514_516del	c.3250dup	COL4A3	c.3829G>A
									p.(T172del)	p.(V1084Gfs*12) (A)		p.(G1277S) (B)
10-1e	M	Famb	4	NS, MH	FSGS	Cs, CsA −	ESRD at 12 years	NPHS2f	c.274G>T	c.506T>C	COL4A3	c.4504T>C
									p.(G92C) (B)	p.(L169P) (B)		p.(F1502L) (C)
10-2	F	Famg	2	NS	MCD	Cs, CsA ±	Normal Cr at 18 years	NPHS2f	c.274G>T	c.506T>C	COL4A3	—
									p.(G92C) (B)	p.(L169P) (B)
253-1	F	Famb	32	NS, MH	FSGS*	Cs, CsA −	ESRD at 33 years	INF2	c.2065C>T		COL4A3	c.4028-3C>A p.(V1344_G1385del) (A)
									p.(R689W) (I)
253-2	M	Famh	39	Non-nephrotic proteinuria, MH	FSGS	—	ESRD at 51 years	INF2	—		COL4A3	c.4028-3C>A p.(V1344_G1385del) (A)
253-3	M	Fami	—	—	NP	—	Normal Cr at 61 years	INF2	—		COL4A3	c.4028-3C>A p.(V1344_G1385del) (A)
253-4	F	Famj	U	MH	NP	—	Normal Cr at 52 years	INF2	—		COL4A3	c.4028-3C>A p.(V1344_G1385del) (A)
253-5	F	Famc	—	—	NP	—	Normal Cr at 63 years	INF2	c.2065C>T		COL4A3	—
									p.(R689W) (I)

Abbreviations: CKD, chronic kidney disease; CNF, congenital nephrotic syndrome of Finnish type; CNS, congenital nephrotic syndrome; CP, cyclophosphamide; Cr, creatinine; Cs, corticosteroids; CsA, cyclosporin A; DMS, diffuse mesangial sclerosis; ESRD, end-stage renal disease; F, female; Fam, familial case; FSGS, focal segmental glomerulosclerosis; FSGS*, mesangioproliferative lesions with FSGS; M, male; MAL, microalbuminuria; MCD, minimal change disease; MG, mutation group; MH, microhematuria; MMF, mycophenolate mofetil; NP, not performed; NS, nephrotic syndrome; Sp, sporadic case; U, unknown.

Therapy effect categories: (−), no response; (±), partial reduction of proteinuria. Mutations on these genes were classified according to Genebank Accession numbers: NG_013356.2, NM_004646.2 and NP_004637.1 (NPHS1); NG_007535.1, NM_014625.2 and NP_055440.1 (NPHS2); NG_009272.1, NM_024426.3 and NP_077744.3 (WT1); NG_027684.1, NM_022489.3 and NP_071934.3 (INF2); NG_011476.1, NM_004621.5 and NP_004612.2 (TRPC6); NG_011591.1, NM_000091.4 and NP_000082.2 (COL4A3). The nomenclature used in this study for the description of sequence variants in DNA and protein is in accordance with the Human Genome Variation Society guidelines and can be found at http://www.hgvs.org/. Mutation groups: A, definitely pathogenic; B, highly likely pathogenic→VS≥11; C, likely pathogenic→5≤VS≤10. Leiden Open Variation Database proband IDs (following the order of the table from top to bottom): 17906, 17907, 19917, 19413, 17908, 17909, 19916, 18450, 18451, 18452, 18453, and 18844.

^aOnly child of consanguineous parents.

^bProband.

^cProband's mother.

^dProband's brother.

^ePatients of the validation cohort.

^fMutations in these genes were previously known in Sanger sequencing.

^gProband's sister.

^hProband's father.

ⁱProband's uncle.

^jProband's aunt.