Nephronophthisis: NPHP4 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 4

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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Genes (1)

Indications

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

Methodology

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

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

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)
WBP

Requirements
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 24 hours of collection. Do not refrigerate or freeze.
DNA, Isolated
DNA

Requirements
Microtainer
3µg
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.

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 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.

How to Order

Requisition Forms