Scientific background:

Summary: The gene SLC34A3 encodes a sodium phosphate transporter located in the apical membrane of proximal tubulus cells. Inactivating mutations result in hyperphosphaturie with hypercalciuria and rickets, which is inherited in an autosomal recessive pattern.

Molecular anatomy: The gene SLC34A3 is expressed exclusively in the kidney where the encoded transporter is found in the apical membrane of proximal tubulus cells.

Interpretation: Loss-of-function mutation in the SLC34A3 gene cause autosomal recessive hypophosphatemic rickets with hypercalciuria. Truncating and missense mutations have been described as pathogenetic relevant.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 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: 

Bergwitz C et al. (2006) SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.
Ichikawa S et al. (2006) Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria.
Lorenz-Depiereux B et al. (2006) Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.
Segawa H et al. (2002) Growth-related renal type II Na/Pi cotransporter.
Tieder M et al. (1985) Hereditary hypophosphatemic rickets with hypercalciuria.
Negri AL et al. (2007) Hereditary hypophosphatemias: new genes in the bone-kidney axis.
Miyamoto K et al. (2007) New aspect of renal phosphate reabsorption: the type IIc sodium-dependent phosphate transporter.
Biber J et al. (2009) Regulation of phosphate transport in proximal tubules.
Forster IC et al. (2006) Proximal tubular handling of phosphate: A molecular perspective.
Murer H et al. (2004) The sodium phosphate cotransporter family SLC34.