Scientific background:

Summary: Mutations of this gene cause primary hypomagnesaemia.

Gene: 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).

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.

Clinical signs: 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.

Epidemiology: Only few families have been described.

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

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

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		10 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

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