Clinical features and genetic analysis of 15 Chinese children with dent disease

Figures & data

Table 1. Clinical features and gene mutations of patients with dent disease.

Patient	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
Group	DD1	DD1	DD1	DD1	DD1	DD1	DD1	DD1	DD1	DD1	DD1	DD1	DD2	DD2	DD2
Sex	Male	Male	Male	Male	Male	Male	Male	Male	Male	Male	Male	Male	Male	Male	Male
Age at onset (years)	8.46	10.4	2.97	4.65	3.66	1.94	3.85	2.9	7.47	1.75	2.99	4.77	5.8	2.5	6.29
Age at diagnosis (years)	9.46	10.57	4.97	8.15	6.5	2.11	7.43	2.93	9.8	5.75	3.49	4.79	12.8	2.67	6.87
Time from onset to diagnosis (months)	12	2	24	42	34	2	43	ND	28	48	6	0.25	84	2	7
24-hour urine protein (mg/kg weight)	40.9	42	51.1	20.37	23.91	13.33	35.8	–	25.96	53.66	34.29	16.9	32.05	65.83	67.39
Urine protein/creatinine ratio (mg/mg)	1.77	4.18	3.02	1.1	2.02	2.28	1.46	5.35	1.59	3.87	2.85	0.82	2.48	4.97	3.46
Urine immunoglobulin (mg/L)	47.47	59.34	55.12	48.98	21.24	22.84	52.33	–	17.21	35.95	31.4	16.52	67.74	66.31	102.45
Urine microalbuminuria (mg/L)	160.97	192.71	252.11	104.3	84.07	137.2	188.29	–	104.63	124	129.73	37.86	230	258.7	267.45
Urine transferrin (mg/L)	20.91	19.92	31.63	15.03	11.68	14.02	21.53	–	14.43	9.68	16.06	5.36	25.12	31.32	36.07
Urine α1 microglobulin (mg/L)	286	272	413	303	133	166	190	–	139	275	188	56.6	331	388	415
Urine β2 microglobulin (mg/L)	34.8	210.8	95.5	35.96	77	56.7	115	–	24.34	72.48	52.47	17.8	102.5	196.5	188
Urine retinol-binding protein (mg/L)	5.84	6.01	5.79	6.6	7.12	8.18	8.13	–	9.91	133.98	8.27	9.59	4.95	4.37	3.51
Ratio of small-molecule proteinuria	0.587	0.643	0.603	0.672	0.65	0.57	0.544	–	0.56	0.739	0.584	0.584	0.576	0.623	0.599
Urine calcium/urinary creatinine ratio (mg/mg)	0.49	–	0.539	0.35	0.288	0.087	0.11	0.078	0.69	0.53	0.46	0.46	0.14	0.58	0.49
24-hour urinary calcium (mmol/kg)	0.25	–	0.19	0.14	0.04	–	–	–	0.29	–	0.17	0.2		0.13	0.11
Hypophosphatemia	N	N	N	N	N	N	N	N	N	N	N	N	N	Y	Y
Metabolic acidosis	Y	N	N	Y	Y	N	N	N	N	Y	N	Y	Y	Y	Y
Growth deficiency	N	N	N	N	N	N	N	N	N	N	N	N	Y	N	N
Glucosuria	N	N	N	N	N	N	N	N	N	Y	N	N	Y	N	N
Language development delay	N	N	Y	N	N	N	N	N	N	N	N	N	N	N	N
Renal ultrasound	Normal	Normal	Normal	Normal	Normal	Normal	Enhanced renal cone echo	Enhanced renal cone echo	Normal	Normal	Normal	Medullary sponge kidney	Normal	Normal	Normal
Renal pathology	FSGS	MCL	–	–	MCL	–	MCL	–	MCL with small focal acute tubular injury	–	–	–	MCL	–	–
Gene with mutation	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	CLCN5	OCRL1	OCRL1	OCRL1
Type of mutation	Missense	Missense	Missense	Missense	Frameshift	Frameshift	Frameshift	Frameshift	Frameshift	Nonsense	Nonsense	Nonsense	Missense	Missense	Missense
Nucleotide	c.1756C > T	c.1166T > G	c.1756C > T	c.1618G > A	c.407delT	c.1702_c.1703insC	c.137delC	c.665_666delGGinsC	c.2200delG	c.776G > A	c.1609C > T	c.1152G > A	c.1477C > T	c.952C > T	c.198A > G
Protein	p.Arg586Trp	p.L389R	p.Arg586Trp	p.Gly540Arg	p.L136fs	p.T568Tfs*30	p.A46fs	p.G222Afs*32	p.E734fs*14	p.W259*	p.R537*	p.W384*	p.R493W	p.R318C	p.Q66=
Segregation	de novo	Maternal	Maternal	Maternal	Maternal	Maternal	Maternal	Maternal	Maternal	Maternal	Maternal	Maternal	–	de novo	Maternal
ACMG hazard level	Pathogenic	Uncertain	Likely pathogenic	Likely pathogenic	Likely pathogenic	Likely pathogenic	Likely pathogenic	Likely pathogenic	Likely pathogenic	Pathogenic	Pathogenic	Likely pathogenic	Pathogenic	Pathogenic	Uncertain
Novel/recurrent mutation	Recurrent	Novel	Recurrent	Recurrent	Novel	Novel	Novel	Novel	Novel	Recurrent	Recurrent	Recurrent	Recurrent	Recurrent	Novel
References	[5,16,22–24,31–34]		[5,16,22–24,31–34]	[21]						[16]	[5,23,35,36]	[37]	[5,11,16,38]	[16,17,26,39,40]

DD: Dent disease; N: No; Y: Yes; FSGS: focal segmental glomerulosclerosis; MCL: minimal change lesion.

Figure 1. Structural diagram of the protein structure of three missense variants of the CLCN5 gene (p.Gly540Arg, p.Leu389Arg, and p.Arg586Trp).

Figure 2. Structural diagram of the protein structure of two missense variants of the OCRL1 gene (p.Arg493Trp, p.Arg318Cys).

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Data availability statement

The data used and/or analyzed during the current study are available from the corresponding author upon reasonable request.