Nephronophthisis, an autosomal recessive cystic kidney disease, is the most frequent monogenic cause of renal failure in childhood. There are four forms of nephronophthisis caused by mutations in four different genes. Clinically, there is a statistically different age at onset at end-stage renal disease: terminal renal failure develops at median ages of 13 years, 1 year, 19 years, and 11-34 years in NPHP1, NPHP2, NPHP3, and NPHP4 respectively. Hallmarks of familial nephronophthisis are tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys. The histology in later stages of NPH always merges into a chronic sclerosing tubulointerstitial nephropathy, which is found in chronic renal failure of all origins.
In one study, most individuals with adolescent nephronophthisis (NPHP3) suffered from anemia when they first came to medical attention. Onset of terminal renal failure occurred significantly later (median age, 19 years) than in juvenile nephronophthisis (median age, 13.1 years). Histologic findings in adolescent nephronophthisis are generally not distinguishable from those of juvenile nephronophthisis. Renal pathology in adolescent NPHP is characterized by alterations of tubular basement membranes, tubular atrophy and dilatation, sclerosing tubulointerstitial nephropathy, and renal cyst development predominantly at the corticomedullary junction.
Mutations in the NPHP3 gene (3q22) cause NPHP3. Mutations have been found in NPHP3 in families with isolated nephronophthisis and in families with nephronophthisis with associated hepatic fibrosis or tapetoretinal degeneration. Studies have shown that the protein product of the NPHP3 gene interacts with the protein products of NPHP1 and NPHP2.
Click here for the OMIM summary on this condition.
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
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
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 Emory Genetics Laboratory, 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.
- 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.