The index case is a male who began control in our center at the age of 19 years for presenting a picture of poor general condition and fatigue for six months with alteration of renal function (creatinine 1.8 mg/dl).
He had hyperuricemia of five years of evolution without episodes of gouty crisis, which controlled with allopurinol (100 mg/day).
Renovesical ultrasound showed decreased size of both kidneys (9-10 cm) and urine sediment showed no proteinuria or hematuria.
A renal biopsy showed nonspecific changes: 4 glomeruli were normal and 3 were in the wafer, the tubules had an atrophic aspect and lymphomononuclear infiltrate.
The vessels were not affected and immunofluorescence was negative.
1.
The patient had a renal failure of slow progression and at 39 years a living donor kidney transplant (his wife) was performed without incidents.
At 42 years of age, the patient has very stable renal function with baseline creatinine levels of 1.5 mg/dl and is being treated with allopurinol 100 mg/day.
Family history includes several members with renal involvement and hyperuricemia, with different degrees of renal failure and clinical polyuria and polydipsia.
A brother (III-2) with chronic kidney disease and hyperuricemia was admitted at age 47.
Another sister (III-1), also with chronic kidney disease and hyperuricemia (at 35 years old has a creatinine of 1.8 mg/dl).
The mother (II-4) of the three siblings, also with chronic kidney disease, started dialysis at age 34 and died at age 66.
1.
The diagnosis of juvenile familial hyperuricemic nephropathy was made by mutational analysis of the UMOD gene by direct sequencing of the 10 coding exons (exon 2-exon 11) from the genomic DNA index.
Mutational analysis allowed the identification of the sequence variant c.606G>C (p.W202C) in heterozygosis.
This variant is located in exon 3 of the UMOD gene and has not been previously described in the literature, although another mutation that alters the same amino acid [c.605G>C) (p.W202S) has been described.
The c.606G>C variant (p.W202C) was not identified in more than 200 analyzed control chromosomes and alters the tryptophan amino acid 202 that is fully conserved in orthologous proteins.
We also studied the segregation of this variant in the family and identified that it is caused by all affected members.
Distinct biofertilisation algorithms (Condel, Sift Polyphen) predict that this is a pathogenic mutation.
Therefore, we conclude that the c.606G>C variant (p.W202C) was with very high probability the pathogenic mutation causing the disease.
1.
The diagnosis of this pathogenic mutation allowed the study of certain young relatives, such as individuals IV:1 (affected) and IV:2 (unaffected).
