Familial juvenile nephronophthisis (FJN) is a hereditary cystic kidney disease. Children may present with polyuria, polydipsia, anemia and growth retardation. It is the most common hereditary cause of chronic renal failure in children, accounting for some 6 – 10% of juvenile ESRD¹. Although genetically heterogeneous, the genetic basis of the majority of nephronophthisis was discovered in 1997 when alterations in the NPHP1 gene were found in approximately 85% of children with the purely renal form^2,3. In approximately 80% of patients, a large (290kb) deletion was found to be responsible for the disease⁴. It is inherited in an autosomal recessive fashion.

Athena is pleased to offer molecular testing for the common deletion in NPHP1 to aid in the diagnosis of patients who have symptoms consistent with FJN. Order NPH1 (FJN) Molecular Analysis (Unit Code 750).

Indications for Testing

• Confirmation in patients presenting with symptoms of nephronophthisis
• In children with secondary enuresis
• In place of renal biopsy to confirm presumptive diagnosis of nephronophthisis

Nephronophthisis diagnostic algorithm (after Hildebrandt, et al., ref. 5)

Clinical picture suggestive of NPH (polyuria, polydipsia, drinking at night, secondary enuresis, growth retardation, anemia, elevated serum creatinine)

Perform Renal Ultrasound (normal kidney size, hyperechogenicity, loss of corticomedullary differentiation, corticomedullary cysts)

Initiate Molecular Genetic Diagnostics (PCR for homozygous deletion in NPHP1; DNA material from blood sample of affected individual and parents)

NPH1 (FJN) Molecular Analysis from Athena Diagnostics Homozygous NPHP1 Deletion?

Present   Absent

Diagnosis of juvenile nephronophthisis (NPH1) firmly established     Initiate test for heterozygosity with polymorphic markers

REFERENCES

1. Antignac, C. et al., (1998) Nephronophthisis. In: Cameron, D. et al. (eds) Clinical nephrology. Oxford University Press, Oxford and New York, pp. 2417-2426.
2. Hildebrandt, F., et al., (1997) A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nature Genet. 17:149-153.
3. Saunier, S., et al., (1997) A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis. Hum. Molec. Genet. 6: 2317-2323.
4. Saunier, S., et al., (2000) Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis. Am. J. Hum. Genet. 66: 778-789.
5. Hildebrandt, F., et al., (2001) Establishing an algorithm for molecular genetic diagnostics in 127 families with juvenile nephronophthisis. Kidney Int. 59:434-445.
6. Omran H, et al., (2001) Evidence for further genetic heterogeneity in nephronophthisis. Nephrol Dial Transplant. 16(4):755-758.