New TRPM6 mutation and management of hypomagnesaemia with secondary hypocalcaemia

Brain Dev. 2015 Mar;37(3):292-8. doi: 10.1016/j.braindev.2014.06.006. Epub 2014 Jun 28.


Background: TRPM6 gene mutation has been reported to cause hypomagnesemia with secondary hypocalcemia (HSH). However, the genotype-phenotype correlation for TRPM6 gene mutations has not been clarified.

Objective: To elucidate the factors underlying the severe neurological complications in HSH and evaluate the potential association between the location of TRPM6 gene mutations and clinical data of HSH.

Methods: A Japanese patient diagnosed with HSH at 10 weeks of age exhibited neurological damage and failed to thrive. Magnesium supplements were therefore started at 12 weeks of age. Mutational analysis of the TRPM6 gene was performed using a direct sequencing method to determine the position and type of mutation. Using the data of 29 HSH patients reported in the literature, linear regression analysis was also performed to examine the association between TRPM6 gene mutation location and HSH onset age, initial serum magnesium and calcium concentrations, and dose of oral magnesium.

Results: A novel stop-codon homozygous mutation [c.4190 G>A] W1397X was identified in exon 26 of the patient's TRPM6 gene. No statistical correlation was found between the location of mutations in the TRPM6 gene and the clinical data for 4 clinical indicators of HSH.

Conclusions: We identified the first Japanese HSH patient with a novel nonsense mutation in the TRPM6 gene. Regression analysis of mutation locations in the protein-coding region of TRPM6 and the reported clinical data for 4 clinical indicators of HSH in 30 HSH patients did not detect a genotype-phenotype correlation.

Keywords: Failure to thrive; Genotype–phenotype correlation; HSH; Magnesium; Mental retardation; TRPM6.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon, Nonsense
  • Female
  • Humans
  • Hypocalcemia / drug therapy
  • Hypocalcemia / genetics*
  • Infant
  • Japan
  • Magnesium Deficiency / congenital
  • Renal Tubular Transport, Inborn Errors / drug therapy
  • Renal Tubular Transport, Inborn Errors / genetics*
  • TRPM Cation Channels / genetics*


  • Codon, Nonsense
  • TRPM Cation Channels
  • TRPM6 protein, human

Supplementary concepts

  • Hypomagnesemia 1, Intestinal