Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Claudin 16

Mutations of this gene cause primary hypomagnesaemia.

Epidemiology

Only few families have been described.

Gene Structure

The gene has a size of 23 kb. It is also known as paracellin-1 (PCLN1). Recent evidence has shown that this gene belongs to a family called claudines. It consists of 5 exons and it is located on chromosome 3 (3q27).

Phenotype

The predominant clinical symptom is hypomagnesemia accompanied by hypercalciuria. This condition predisposes to the development of kidney stones in heterozygous patients. In contrary, in homozygous patients there is nephrocalcinosis and renal failure in childhood.

Pathology

The translation product is a 305 amino acid proteine that consists of 4 transmembrane domains and intracellular amino- and C-termini. The protein is exclusively found in the kidney. Along the nephron it is located in the thick ascending limb of Henle's loop and in the distal convolution where it forms tight junction together with occludin. Obviously it regulates net paracellular magnesium flux.

Test Strategy

Predominant indications for molecular diagnostic are family counseling and improvement of diagnostic precision.

Interpretation

The therapeutic consequences include family counseling and prophylaxis for kidney stone formation.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 10 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Hypomagnesemia with hypercalciuria and nephrocalcinosis
CLDN16

References:

1.

Weber S et al. (2000) Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene.

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2.

Konrad M et al. (2004) Insights into the molecular nature of magnesium homeostasis.

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Update: Sept. 26, 2018