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.
Clinicalfeatures of familial juvenile nephronophthisis (NPHP1) include anemia,polyuria, polydipsia, isosthenuria, and death in uremia. Hypertension andproteinuria are conspicuous in their absence. Excessive urinary loss of sodiumaccounts for the rarity of hypertension. Symmetrical destruction of the kidneysinvolving both tubules and glomeruli (which were hyalinized) is observed. Theage at death ranges from about 4 to 15 years. This is the second most commoncause of childhood chronic renal failure. 65 to 75% of NPHP1 patients exhibitlarge homozygous deletions in the 2q13 region that includes the NPHP1 gene.
Joubertsyndrome is an autosomal recessive multisystem disease characterized bycerebellar vermis hypoplasia with prominent superior cerebellar peduncles(resulting in the 'molar tooth sign,' or MTS, on axial MRI), mentalretardation, hypotonia, irregular breathing pattern, and eye movementabnormalities. Some individuals with JS have retinal dystrophy and/orprogressive renal failure characterized as nephronophthisis. The disorder insuch patients is referred to as cerebellooculorenal syndrome, or CORS.Individuals with a mild form of JS have been shown to have a homozygousdeletion of the NPHP1 gene identical,by mapping, to that in subjects with nephronophthisis alone. Senior-Lokensyndrome, the association of nephronophthisis with autosomal recessiveretinitis pigmentosa, has been observed in patients with homozygous deletion ofthe NPHP1 gene.
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This test is indicated for:
- Confirmation of a clinical/biochemical diagnosis offamilial juvenile nephronophthisis
- Carrier testing in adults with a family history of familial juvenile nephronophthisis
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.
- Custom diagnostic mutation analysis is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.