title: A novel mutation in CLDN16 results in rare familial hypomagnesaemia with hypercalciuria and nephrocalcinosis in a Chinese family.
abstract: BACKGROUND
  Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessively inherited disease characterized by excessive wasting of renal tubular magnesium and calcium. FHHNC is associated with various mutations in CLDN16 and CLDN19.
  
  
  METHODS
  Two children from a consanguineous family of Chinese Han origin demonstrated manifestations of rickets, polyuria, polydipsia, hematuria and failure to thrive. Hypomagnesaemia (0.49-0.50mmol/L), hypercalciuria or a trend to hypercalciuria (24hour urine calcium: 3.8-5.1mg/kg/day), and secondary hyperparathyroidism (serum PTH level: 94.7-200pg/mL) were revealed upon laboratory examination. Using targeted next-generation sequencing and subsequent confirmation by Sanger sequencing, a novel homozygous mutation was identified in the CLDN16 gene of both FHHNC patients. This specific mutation, a 16bp deletion followed by a 23bp insertion in exon 3, led to the generation of a premature termination codon. The parents and an unaffected sister were all heterozygous carriers of this mutation.
  
  
  CONCLUSIONS
  We detected a novel mutation in CLDN16 for the first time. The clinical and genetic findings from this study will help to expand the understanding of this rare disease, FHHNC.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Jian-Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xing
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: limeilzh@sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
mesh_terms: D000293:Adolescent; D002648:Child; D002681:China; D057167:Claudins / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000150:complications*; D008274:Magnesium / Q000097:blood*; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000150:complications*; D010375:Pedigree
chemical_list: D057167:Claudins; C502010:claudin 16; D008274:Magnesium
keywords: CLDN16; Hypercalciuria; Hypomagnesaemia; Nephrocalcinosis; Rickets