Glomerulopathy with Fibronectin Deposits via the FN1 Gene

Glomerulopathy with fibronectin deposits (GFND) is characterized by proteinuria, microscopic hematuria, and hypertension with age-related penetrance (Castelletti et al. 2008; Ohtsubo et al 2016). Patients progress to end-stage renal failure in the second to fifth decade of life. Pathologic examination revealed enlarged glomeruli with deposits in the mesangium and subendothelial space.

Glomerulopathy with fibronectin deposits is an autosomal dominant disorder with age-related penetrance and so far the FN1 gene is the only causative gene found for the disease (Castelletti et al. 2008; Ohtsubo et al 2016). The FN1 gene (46 coding exons) encodes fibronectin, a glycoprotein involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. To date, documented genetic defects of FN1 include missense and one small in-frame deletion (Human Gene Mutation Database). Large deletions/duplications have not been reported to date.

In a study of 15 unrelated families with glomerulopathy with fibronectin deposits, sequencing of the FN1 gene identified three different heterozygous missense variants that co-segregated with the disease in six families (40%) (Castelletti et al. 2008).

In another study of 12 unrelated families with glomerulopathy with fibronectin deposits, sequencing for the FN1 gene identified six different heterozygous variants in all of 12 families (100%) (Ohtsubo et al. 2016).

This test provides full coverage of all coding exons of the FN1 gene 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 full 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).