title: First report of a novel missense CLDN19 mutations causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a Chinese family.
abstract: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder caused by mutations in the CLDN16 or CLDN19 genes, encoding claudin-16 and claudin-19 in the thick ascending limb of Henle's loop. In patients with claudin-19 mutations, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described. In this report, we presented a 12-year-old girl with rickets, polyuria, and polydipsia. She was the daughter of consanguineous parents, and she had a history of recurred hypocalcemic and hypomagnesemic tetany. On physical examination, bilateral horizontal nystagmus and severe myopia were detected. Laboratory examination revealed hypomagnesemia, hypocalcemia, hypercalciuria, nephrocalcinosis, and renal stone. A clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the ocular findings. DNA analysis revealed a novel homozygous missense mutation c.241C>T in the CLDN19 gene. In conclusion, in a patient with hypomagnesemia, hypercalciuria, nephrocalcinosis, and ocular findings, a diagnosis of FHHNC caused by claudin-19 mutation should be considered. This is the first study of FHHNC in Chinese population. Our findings of the novel mutation c.241C>T in exon 2 add to the list of more than 16 mutations of CLDN19 gene reported.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, The Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Pang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Li
authors.forename: Jingjun
authors.initials: J
authors.lastname: Li
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wu
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: Jin
authors.initials: J
authors.lastname: Dong
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002681:China; D057167:Claudins / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics*; D006996:Hypocalcemia / Q000235:genetics*; D008275:Magnesium Deficiency / Q000151:congenital* / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009397:Nephrocalcinosis / Q000235:genetics*; D059606:Polydipsia / Q000235:genetics; D011141:Polyuria / Q000235:genetics; D012279:Rickets / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: C508912:CLDN19 protein, human; D057167:Claudins