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.
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Acknowledgments
This study was supported by a Grant from The Ministry of Science and Technology of the People’s Republic of China (National Science and Technology Major Projects for “Major New Drugs Innovation and Development” 2008ZX09312-016). We also thank National Natural Science Foundation of China (No.81070687 and 81170805), Beijing Natural Science Foundation (No. 7121012), Scientific Research Foundation of Beijing Medical Development (No. 2007-3029), and National Key Program of Clinical Science (WBYZ2011-873) for their support.
Conflict of interest
Tao Yuan, Qianqian Pang, Xiaoping Xing, Xi Wang, Yuhui Li, Jingjun Li, Xueyan Wu, Mei Li, Ou Wang, Yan Jiang, Jin Dong, and Weibo Xia declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This study was approved by the Department fo Scientific Research of PUMCH. All participants signed informed consent at the time of their participation in the study.
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Tao Yuan and Qianqian Pang contributed equally to this work.
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Yuan, T., Pang, Q., Xing, X. et al. First Report of a Novel Missense CLDN19 Mutations Causing Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis in a Chinese Family. Calcif Tissue Int 96, 265–273 (2015). https://doi.org/10.1007/s00223-014-9951-7
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DOI: https://doi.org/10.1007/s00223-014-9951-7