Nephronophthisis: NPHP3 Gene Deletion/Duplication

Condition Description

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.

Nephronophthisis 3

Inone study, most individuals with adolescent nephronophthisis (NPHP3) sufferedfrom anemia when they first came to medical attention. Onset of terminal renalfailure occurred significantly later (median age, 19 years) than in juvenilenephronophthisis (median age, 13.1 years). Histologic findings in adolescentnephronophthisis are generally not distinguishable from those of juvenilenephronophthisis. Renal pathology in adolescent NPHP is characterized byalterations of tubular basement membranes, tubular atrophy and dilatation,sclerosing tubulointerstitial nephropathy, and renal cyst developmentpredominantly at the corticomedullary junction.

Mutationsin the NPHP3 gene (3q22) cause NPHP3.Mutations have been found in NPHP3 infamilies with isolated nephronophthisis and in families with nephronophthisiswith associated hepatic fibrosis or tapetoretinal degeneration. Studies haveshown that the protein product of the NPHP3 gene interacts with the proteinproducts of NPHP1 and NPHP2.

Click here for the OMIM summary on this condition.

Genes (1)


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of adolescent nephronophthisis in individuals who have tested negative for sequence analysis
  • Carrier testing in adults with a family history of adolescent nephronophthisis who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)

EDTA (Purple Top)
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
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

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 NPHP3 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.

How to Order

Requisition Forms