Invitae Nephronophthisis Panel


Test description

The Invitae Nephronophthisis Panel analyzes 12 genes that are associated with nephronophthisis (NPHP). These genes are involved in the structure and function of the ciliary apparatus. Cilia are necessary for proper cellular motility, for the movement of material around a cell, and for chemical signaling pathways. Pathogenic variants in any of these genes result in ciliary dysfunction and are likely to disrupt signaling pathways in the kidneys, ultimately leading to established renal failure.

Identification of the molecular basis of disease in an affected individual may confirm diagnosis and encourage testing of additional family members to inform reproductive risk. Although there is no treatment currently available to halt the onset of renal failure, a diagnosis may also help prepare the patient, family, and clinician for the possibility of renal transplantation.

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Primary panel (12 genes)


CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.

Alternative tests to consider

Nephronophthisis is a member of a class of disorders called ciliopathies. Ciliopathies are caused by pathogenic variants in genes that affect the function of cilia—the hair-like structures on the surface of cells. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone.

The Invitae Sensory Ciliopathies Panel has been designed to provide a broad genetic analysis of this class of disorders and may be considered as an alternative to testing for a specific disorder. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

Nephronophthisis (NPHP)

Nephronophthisis is characterized by renal cysts, inflammation, and fibrosis, all leading to early onset end-stage renal disease. Characteristic renal histology shows corticomedullary cysts, tubular basement membrane disruption, and tubulointerstitial nephropathy. Additional symptoms related to the renal disease present in NPHP include polyuria, polydipsia, fatigue, and anemia. Extra-renal manifestations are present in approximately 10% of individuals with NPHP and often involve the eye, brain, heart, and liver. Individuals with extra-renal involvement present with phenotypes that are more similar to other ciliopathy-related disorders, such as Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, and Meckel-Gruber syndrome. Extra-renal findings can include retinal degeneration, retinitis pigmentosa, cerebellar vermis hypoplasia, intellectual disability, ataxia, liver fibrosis, ventricular septal defect, molar tooth sign, and cone-shaped epiphyses.

This panel will identify variants in approximately 30% of individuals with a clinical diagnosis of NPHP. In 70% of individuals with a clinical diagnosis of NPHP, no pathogenic variants will be identified. These data suggest that additional genes associated with NPHP are still unidentified.

Gene% of NPHP attributed to pathogenic variants in this gene
CEP290 ~1%
GLIS2 less than 1%
INVS ~1%
IQCB1 ~3%
NEK8 less than 1%
NPHP1 ~25%
NPHP3 ~1%
NPHP4 ~2%
RPGRIP1L less than 1%
TMEM67 unknown, rare
TTC21B unknown, rare
XPNPEP3 unknown, rare

Nephronophthisis is inherited in an autosomal recessive, oligogenic manner.

Nephronophthisis is a fully penetrant disorder with symptoms that begin to manifest in infancy, childhood, or adolescence, based on the specific subtype present. Morbidity and mortality is related to the development of end stage renal disease (ESRD) and hepatobiliary disease. Most patients develop ESRD by the age of 13.

The incidence of nephronophthisis in live births is estimated at approximately 1 in 50,000 in Canada and 1 in 922,000 in the United States.

Radiology findings are typically used to establish a clinical diagnosis of NPHP. Genetic testing should be considered to determine the molecular cause of disease in individuals with a clinical or suspected diagnosis of NPHP. Genetic testing can also be used to clarify uncertain radiology results, establish recurrence risk, provide disease prognosis, and potentially screen living donors for transplantation. Some of these genes have also been associated with extra-renal features such as retinal dystrophy, liver fibrosis, and pancreatic cysts. Identification of mutations in these genes can help to prepare the patient and clinician for the possibility of the involvement of other organ systems and may direct patient care.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CEP290* NM_025114.3
GLIS2 NM_032575.2
INVS NM_014425.3
IQCB1 NM_001023570.2
NEK8 NM_178170.2
NPHP1 NM_000272.3
NPHP3 NM_153240.4
NPHP4 NM_015102.4
RPGRIP1L NM_015272.2
TMEM67 NM_153704.5
TTC21B NM_024753.4
XPNPEP3 NM_022098.3

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.