Novel TRPM6 Mutations in Familial Hypomagnesemia with Secondary Hypocalcemia
Novel TRPM6 Mutations in Familial Hypomagnesemia with Secondary Hypocalcemia
复制标题
家族性低镁血症伴继发性低钙血症中的新 TRPM6 突变
DOI：
10.1159/000350886
复制
发表时间：
2013-01-01
影响因子：
4.2
通讯作者：
Xia, Weibo
中科院分区：
文献类型：
--
作者：
Zhao, Zhen;Pei, Yu;Xia, Weibo
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. Conclusion: Our results suggested that the compound heterozygous mutations in TRPM6 were responsible for HSH in the Chinese family.
