Scientific background:

Summary: This gene is one of two genes involved in cystinuria.

Gene: The gene SLC7A9 formerly named b(0,+)AT is localized on chromosom 19 (19q13.1). It is about 40kb in size an consits of 13 exons, 12 of them translated.

Pathology: The protein product of this gene is in its functional form highly glycosilated. It forms a heterodimer with a big subunit. This heterodimer is the transporter for dibasic amino acids. It can be found on the luminal membrane of enterocyzes and proximal tubulus cells. The resultant defect in transport refers not only to cystein but other dibasic amino acids lysine and arginine are effected too. But only the transport defect of cystine gains clinical importance.

Clinical signs: The most important symptome is cystinuria. This leads to cysine stone formation because of the bad solubility of cystine in urinary environment. Later on in the history of the disease there might be recurrent urinary infections dominating the clinical picture. End stage renal failure is rare. According to the classical differention of cystinuria mutations in this small subunit may be classified as type 2 and 3 (ROSENBERG).

Epidemiology: Cystinuria is not rare. The prevalence is 1:7.000

Interpretation: The importance of the genetic testing of this gne can be seen in family consuling and early prophylaxis.

Test strategy: Confirmation of the diagnosis when cystinuria is suspected. Family screening if a patient in the family is known.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		medium
		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.
	research test	Method		Gene dosage measurements
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	Of the gene rearrangements, this method is useful to detect large deletions or duplications.

Literature: 

Langman CB et al. (2004) The molecular basis of kidney stones.
Goodyer P et al. (2004) The molecular basis of cystinuria.
Dello Strologo L et al. (2006) Cystinuria.