Scientific background:

Summary: The OCRL gene encodes phosphatidylinositol 4,5-bisphosphate-5-phosphatase and may be involved in such x-linked recessive disorders as Lowe and Dent disease.

Molecular anatomy: The gene encodes en enzyme, 4,5-bisphosphate-5-phosphatase, which is ubiquitously distributed in the Golgi apparatus.

Pathology: Pathomechanisms theat link the mutation to the clenical features are not fully understood yet. It is discussed that dysfunction may alter a cell's polarity, which seems to be of particular importance in renal tubular and corneal cells. Also, it is observed that patients urinary megalin excretion is low, which indicates a disturbed recycling process.

Clinical signs: Two different diseases are associated with mutations of the OCRL1 gene. These are Lowe syndrome and Dent disease. The latter however occurs only in some specific mutations.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		20 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.

Literature: 

Hoopes RR et al. (2005) Dent Disease with mutations in OCRL1.
AURICCHIO S et al. (1961) [Primary tubulopathies. III. A case of oculo-cerebro-renal syndrome (Lowe syndrome)]
Lowe M et al. (2005) Structure and function of the Lowe syndrome protein OCRL1.
Pendaries C et al. (2003) Phosphoinositide signaling disorders in human diseases.
Loi M et al. (2006) Lowe syndrome.
Choudhury R et al. (2005) Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network.
Faucherre A et al. (2005) Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology.
Faucherre A et al. (2003) Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network.
Suchy SF et al. (2002) The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization.