Nephronophthisis,an autosomal recessive cystic kidney disease, is the most frequent monogeniccause of renal failure in childhood. There are four forms of nephronophthisiscaused by mutations in four different genes. Clinically, there is astatistically different age at onset at end-stage renal disease: terminal renalfailure develops at median ages of 13 years, 1 year, 19 years, and 11-34 yearsin NPHP1, NPHP2, NPHP3, and NPHP4 respectively. Hallmarks of familialnephronophthisis are tubular basement membrane disruption, interstitiallymphohistiocytic cell infiltration, and development of cysts at thecorticomedullary border of the kidneys. The histology in later stages of NPHalways merges into a chronic sclerosing tubulointerstitial nephropathy, whichis found in chronic renal failure of all origins.
Mutationsin the NPHP4 gene (1p36) causenephronophthisis 4 (NPHP4), which has also been referred to as jeuvenile nephronophthisis.In these families, end-stage renal disease commenced within a wide age range,11 to 34 years. The NPHP4 protein has been shown to interact with the NPHP1protein. Mutations in NPHP4 have beenassociated with Senior-Loken syndrome-4, the association of nephronophthisiswith autosomal recessive retinitis pigmentosa.
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This test is indicated for:
- Confirmation of a clinical/biochemical diagnosis of jeuvenile nephronophthisis/NPHP4 in individuals who have tested negative for sequence analysis
- Carrier testing in adults with a family history of jeuvenile nephronophthisis/NPHP4 who have tested negative for sequence analysis
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.
- Sequencing analysis of the NPHP4 gene is available and is required before deletion/duplication analysis.
- Custom diagnostic mutation analysis is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenataltesting is available to couples who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.