title: New TRPM6 mutation and management of hypomagnesaemia with secondary hypocalcaemia.
abstract: 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.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Koujyu
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Povalko
authors.affiliation: Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yatsuga
authors.affiliation: Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nishioka
authors.affiliation: Department of Biostatistics, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kakuma
authors.affiliation: Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Toyojiro
authors.initials: T
authors.lastname: Matsuishi
authors.affiliation: Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan. Electronic address: yasukoga@med.kurume-u.ac.jp.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Koga
mesh_terms: D018389:Codon, Nonsense; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000188:drug therapy / Q000235:genetics*; D007223:Infant; D007564:Japan; D008275:Magnesium Deficiency / Q000151:congenital; D015499:Renal Tubular Transport, Inborn Errors / Q000188:drug therapy / Q000235:genetics*; D050053:TRPM Cation Channels / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human
keywords: Failure to thrive; Genotype–phenotype correlation; HSH; Magnesium; Mental retardation; TRPM6