Table 2.
The genotype–phenotype correlation in 25 patients with a known genetic disease
| Genetic diagnosis | Number of cases | Sex | Onset-age | Genetic testing | Phenotype | |
|---|---|---|---|---|---|---|
| Renal | Extrarenal | |||||
| Genes of failed urinary acidification and hypercalciuria | ||||||
| Dent disease | 4 | |||||
| N1 | M | 2 years 2 months | OCRL1 c.556 A > T p.K186X, 716 | NC hypercalciuria LMWP | Growth and psychomotor retardation | |
| N2 | M | 3 years 3 months | OCRL1 c.218 T > A p.L73X, 829 |
NC Hypercalciuria LMWP |
Growth retardation | |
| N3 | M | 4 years 11 months | CLCN5 c.478 T > C p.C160R |
NL + NC Hypercalciuria LMWP |
Growth retardation | |
| N4 | M | 14 years | CLCN5 c.2131 T > C p.C711R | NC hypercalciuria LMWP | - | |
| Distal renal tubular acidosis | 6 | |||||
| N5 | M | 12.5 years | SLC4A1 c.2102 G > A p.G701D |
NC CKD2 LMWP |
Growth retardation, knock knees, hypokalemia | |
| N6 | F | 9 months | SLC4A1 c.1765 C > T p.R589C | NC | Growth retardation, hypokalemia | |
| N7 | M | 6 years | SLC4A1 c.1766 G > A p.R589H |
NL hypercalciuria LMWP |
Growth retardation, knock knees, hypokalemia | |
| N8 | F | 1 years 8 months |
ATP6V1B1 c.1153 C > A p.P385T c.806C > T p.P269L |
NC | Growth retardation, hypokalemia, LMWP | |
| N9 | F | 3 months | ATP6VOA4 c.1899 C > A p.Y633X, 208 hom | NC | Growth retardation, hypokalemia, ASD | |
| N10 | M | 3 years 11 months | SLC4A1 c.1765 C > T p.R589C | NL + NC hypercalciuria LMWP | Growth retardation, hypokalemia | |
| X-1inked dominant hypophosphate | 1 | |||||
| N11 | F | 3 years 9 months | PHEX c.1735 G > A p.G579R | NC | Growth retardation, Bow legs, psychomotor retardation, hypophosphatemia | |
| Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis | 1 | |||||
| N12 | F | 2 years 11 months | CLDN16 loss1 (exon: 3) c.427 + 5 (IVS2) G > A | NC | Hypomagnesemia | |
| Infantile hypercalcaemia | 1 | |||||
| N13 | F | 11 months | CYP24A1 c.1310 C > A p.P437H hom |
NC CKD2 LMWP |
Growth and psychomotor retardation, hypercalcemia, muscle weakness | |
| Genes of hyperuricosuria, cystinuria, hyperglycinuria | ||||||
| Cystinuria | 2 | |||||
| N14 | M | 10 months |
SLC3A1 c.541C > T p.R181W c.850 G > C p.D284H c.1173 C > G p.D391E |
NL, l-cystine stone | Growth retardation, ASD | |
| N15 | M | 6 years 7 months |
SLC7A9 c.376 G > A p.A126T c.149 T > G p.V50G |
NL, l-cystine stone | Growth retardation | |
| Primary hyperoxaluria | 3 | |||||
| N16 (PH1) | M | 4 months |
AGXT c.25 _ c.26 insC p.T9Tfs * 159 c.121 G > A p.G41R |
NL + NC, increased excretion of oxalic acid | Renal rickets | |
| N17 (PH3) | M | 11 months |
HOGA1 c.834 + 1 (IVS6) G > T c.356 T > G p.V119G |
NL, CaOx stone | Growth retardation | |
| N18 (PH3) | M | 13 months |
HOGA1 c.103 A > G p.I35V c.845 G > A p.R282H |
NL, CaOx stone | Growth retardation | |
| Familial glycosuria | 1 | |||||
| N19 | M | 6 months |
SLC6A19 c.284 G > Cp.R95P c.461 C > T p.P154L |
NL | Psychomotor retardation, ASD | |
| Other genes | ||||||
| Kabuki syndrome | 3 | |||||
| N20 | M | 9 months | KMT2D c.15113_c.15115 del AGG p.E5038_G5039delinsG | NL hypercalciuria | Growth and psychomotor retardation, facial dysmorphism, ASD | |
| N21 | M | 1 years 8 months | KMT2D c.6595 delT p.Y2199fs | NL | Growth and psychomotor retardation, facial dysmorphism, ASD + VSD + PH | |
| N22 | M | 8 years | KMT2D C.15686 dupG P.C5230Lfs*5 | NC hypercalciuria LMWP | Growth and psychomotor retardation, facial dysmorphism, VSD | |
| Arboleda-Tham syndrome | 1 | |||||
| N23 | M | 3 months | KAT6A c.3070 C > T p.R1024X, 981 | NL signal hypercalciuria | Growth and psychomotor retardation, facial dysmorphism + ASD | |
| Autosomal dominant polycystic kidney disease | 1 | |||||
| N24 | M | 8 years | PKD1 c.9806 G > A p.R3269Q | NL + NC | Renal cyst + ASD | |
| CNV | 1 | |||||
| N25 | M | 3 months | CNV chr10: 130378377–135427935 q26.2–q26.3 | NL + NC CKD2 | Growth and psychomotor retardation, VUR + NB/facial dysmorphism | |
Normal urinary values in spot urine samples and normal urinary values in 24-h urine collection: urine calcium-to-creatinine ratio: < 7 months < 0.86, 7–18 months < 0.60, 19 months–6 years < 0.42, > 6 years < 0.20 (mg/mg) or 24-h urinary calcium < 4 mg/kg/24 h. F female, M male, LMWP low-molecular weight protein (the elevated levels of urinary β2-microglobulin and α1-microglobulin), ASD atrial septal defect, VSD ventricular septal defect, PH pulmonary hypertension, CKD chronic kidney disease, VUR vesicoureteric reflux, NB neurogenic bladder, CaOx analysis of stone composition suggests calcium oxalate stone