Nephronophthisis and Senior-Loken Syndrome Panel

Nephronophthisis (NPH) is the most common genetic cause of progressive renal failure in children and young adults. NPH is characterized by polyuria, growth retardation and progressive deterioration of renal function with normal or slightly reduced kidney size (Hildebrandt et al. 1997; Hildebrandt et al. 2009). Nephronophthisis, when associated with Leber Congenital Amaurosis, is known as Senior-Loken syndrome (SLS) (Otto et al. 2005; Hildebrandt et al. 2009). NPH clinical features overlap with a group of diseases known as ciliopathies, which includes Meckel-Gruber Syndrome, Joubert Syndrome, Bardet-Biedl Syndrome and Leber congenital amaurosis.

Nephronophthisis and Senior-Loken syndrome are genetically heterogeneous disorders. NPH and SLS are inherited in an autosomal recessive manner. NPH and SLS are caused by pathogenic variants in genes encoding proteins involved in cilia/centrosome structure, maintenance or function (Hildebrandt et al. 2009). See individual gene test descriptions for more information on molecular biology of gene products.

Sensitivity for Nephronophthisis testing is approximately 30% overall (Hildebrandt et al. 2009). This NGS test can detect the ~279kb deletion in the NPHP1 gene if it is present in the homozygous state.

Approximately 20% of individuals with nephronophthisis have a homozygous deletion encompassing the NPHP1 gene (Hoefele et al 2005; Hildebrandt et al 2009). Gross deletions or duplications that may not be detectable by NGS have been reported in CEP290, NPHP1, TMEM67 and SDCCAG8 (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.4% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).