Scientific background:

Summary: The gene encodes an ion transporter regulator, whose mutations cause hypomagnesaemia with hypocalciuria.

Gene: The gene is about 9,2 kb in size. Alternatively the gene is named sodium-potassium ATPase gamma-1 polypeptide (ATP1G1). It is located on chromosome 11 at position 11q23. It consists 7 exons. Two different isotypes using different promotors are described.

Pathology: The gene is transcribed in pancreas in kidney. In the latter, it is found in the distal convolution. The different isotypes of the protein contain 58 or 66 amino acids. The gene forms a transmembraneous domain and functions as a regulating component of the sodium-potassium ATPase.

Clinical signs: Only one loss-of-function mutation is known so far. In this family also a hypocalciuria occurred. The mode of inheritance was autosomal dominant.

Epidemiology: Epidemiological data concerning this disease are very restricted.

Interpretation: Family counseling is the only therapeutical consequence at the moment.

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: 

Meij IC et al. (2000) Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit.
Kantorovich V et al. (2002) Genetic heterogeneity in familial renal magnesium wasting.