Identification of a Novel Homozygous Missense Mutation in the CLDN16 Gene to Decipher the Ambiguous Clinical Presentation Associated with Autosomal Dominant Hypocalcaemia and Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis in an Indian Family

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHNNC) is a rare autosomal recessive renal tubulopathy disorder characterized by excessive urinary loss of calcium and magnesium, polyuria, polydipsia, bilateral nephrocalcinosis, progressive chronic kidney disease, and renal failure....

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Published in:	Calcified tissue international Vol. 114; no. 2; pp. 110 - 118
Main Authors:	Thapa, Rupesh, Roy, Amaresh, Nayek, Kaustav, Basu, Anupam
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-02-2024 Springer Nature B.V
Subjects:	Amelogenesis imperfecta Biochemistry Biomedical and Life Sciences Calcinosis Calcium (urinary) Cell Biology Dental enamel Diagnosis Endocrinology Epithelial cells Genes Genetic screening Hereditary diseases Hypercalciuria Hypocalcemia Hypomagnesemia Kidney diseases Kidneys Life Sciences Loop of Henle Magnesium Missense mutation Mutation Original Research Orthopedics Parathyroid hormone Polydipsia Polyuria Protein structure Renal failure Autosomal dominant hypocalcaemia Parathyroid hormone Claudin-16 Familial hypomagnesemia with hypercalciuria and nephrocalcinosis
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Summary:	Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHNNC) is a rare autosomal recessive renal tubulopathy disorder characterized by excessive urinary loss of calcium and magnesium, polyuria, polydipsia, bilateral nephrocalcinosis, progressive chronic kidney disease, and renal failure. Also, sometimes amelogenesis imperfecta and severe ocular abnormalities are involved. The CLDN-16 and CLDN-19 genes encode the tight junction proteins claudin-16 and claudin-19, respectively, in the thick ascending loop of Henle in the kidney, epithelial cells of the retina, dental enamel, etc. Loss of function of the CLDN-16 and/or CLDN-19 genes leads to FHHNC. We present a case of FHHNC type 1, which was first confused with autosomal dominant hypocalcaemia (ADH) due to the presence of a very low serum parathyroid hormone (PTH) concentration and other similar clinical features before the genetic investigations. After the exome sequencing, FHHNC type 1 was confirmed by uncovering a novel homozygous missense mutation in the CLDN-16 gene (Exon 2, c.374 T > C) which causes, altered protein structure with F55S. Associated clinical, biochemical, and imaging findings also corroborate final diagnosis. Our findings expand the spectrum of the CLDN-16 mutation, which will further help in the genetic diagnosis and management of FHNNC.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1432-0827 0171-967X 1432-0827
DOI:	10.1007/s00223-023-01142-8