Hypomagnesemia via the FXYD2 Gene

Primary hypomagnesemia is a heterogeneous group of disorders characterized by renal or intestinal Mg(2+) wasting, often associated with disturbances in Ca(2+) excretion (Meij et al. 2000; Viering et al. 2016). This electrolyte imbalance results in muscle cramps, muscle weakness and cardiac arrhythmias. A recurrent missense pathogenic variant in the FXYD2 gene has been reported to cause isolated autosomal dominant hypomagnesemia (Meij et al. 2000; de Baaij et al. 2015).

FXYD2-associated isolated hypomagnesemia is an autosomal dominant disorder (Meij et al. 2000; de Baaij et al. 2015). The FXYD2 gene (five coding exons) encodes the γ-subunit of the Na+-K+-ATPase. To date, only one recurrent missense variant (c.115G>A, p.Gly41Arg; likely a founder effect in the Belgian or Dutch population) in FXYD2 has been reported to cause isolated autosomal dominant hypomagnesemia (Meij et al. 2000; de Baaij et al. 2015).

Detection rate of pathogenic variants in the FXYD2 gene in a large cohort of patients with hypomagnesemia is unknown in the literature because only one recurrent missense variant in FXYD2 has been reported in limited cases of isolated autosomal dominant hypomagnesemia (Meij et al. 2000; de Baaij et al. 2015).

No large deletions or duplications involving FXYD2 have been reported (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the FXYD2 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).