Background: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal\ndisease characterized by tubular disorders at the thick ascending limb of Henle�s loop. It is caused by mutations in\nthe tight junction structural proteins claudin-16 or claudin-19, which are encoded by the CLDN16 and CLDN19\ngenes, respectively. Patients exhibit excessive wasting of calcium and magnesium, nephrocalcinosis, chronic kidney\ndisease, and early progression to end-stage renal failure during infancy.\nCase presentation: We here report the phenotype and molecular analysis of a female Brazilian patient with a novel\nlarge homozygous deletion in the CLDN16 gene. The proband, born from consanguineous parents, presented the first\nsymptoms at age 20. Clinical examination revealed hypocalcemia, hypomagnesemia, nephrocalcinosis, mild myopia,\nhigh serum levels of uric acid and intact parathyroid hormone, and moderate chronic kidney disease (stage 3). She and\nher mother were subjected to CLDN16 and CLDN19 mutational analysis. In addition, the multiplex ligation-dependent\nprobe amplification method was used to confirm a CLDN16 multi-exon deletion. Direct sequencing revealed a normal\nCLDN19 sequence and suggested a large deletion in the CLDN16 gene. Multiplex ligation-dependent probe amplification\nshowed a homozygous CLDN16 multi-exon deletion (E2_E5del). The patient initiated conventional treatment for familial\nhypomagnesemia with hypercalciuria and nephrocalcinosis and progressed to end-stage kidney disease after five years.\nConclusions: This study provides the first report of a large homozygous deletion in the CLDN16 gene causing familial\nhypomagnesemia with hypercalciuria and nephrocalcinosis with late onset of the first symptoms. This description\nexpands the phenotypic and genotypic characterization of the disease. The late-onset chronic kidney disease in the\npresence of a homozygous deletion in the CLDN16 gene reinforces the great variability of genotype-phenotype\nmanifestation in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis
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