title: Novel TRPM6 mutations in familial hypomagnesemia with secondary hypocalcemia.
abstract: BACKGROUND
  Familial hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease characterized by severe hypomagnesemia and hypocalcemia associated with neurological symptoms, including generalized seizures, tetany and muscle spasms, which are refractory to anticonvulsant treatment. The pathophysiological hallmarks of HSH are the impaired intestinal absorption of magnesium accompanied by renal magnesium wasting as a result of a reabsorption defect in the distal convoluted tubule. Mutations in TRPM6, the gene encoding the transient receptor potential cation channel subfamily member 6, have been found to be responsible for this disease. In the present study, we report a Chinese family with 2 sisters affected with severe HSH, and elucidate the characteristics of TRPM6 gene mutations in these 2 patients.
  
  
  METHODS
  We evaluated the clinical, laboratory, and radiographic findings. All 39 TRPM6 exons and flanking exon-intron junctions from genomic DNA were amplified and sequenced in 2 affected members suffering from HSH and their family.
  
  
  RESULTS
  We found two novel mutations in the family, one frameshift mutation (c.1196delC) and one non-sense mutation (c.4577G>A). These mutations were predicted to result in a complete loss of function of TRPM6. Both of the sisters were compound heterozygotes for these mutations.
  
  
  CONCLUSIONS
  Our results suggested that the compound heterozygous mutations in TRPM6 were responsible for HSH in the Chinese family.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, The Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Pei
authors.forename: Xianglan
authors.initials: X
authors.lastname: Huang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Nuo
authors.initials: N
authors.lastname: Si
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
mesh_terms: D044466:Asian People / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D006996:Hypocalcemia / Q000235:genetics*; D008275:Magnesium Deficiency / Q000151:congenital; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics*; D050053:TRPM Cation Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human