Scientific background:

Pathophysiology: The gene product of LMX1B is a LIM-homeodomain transcription factor, which plays a role in skeletal and kidney development. It regulates normal patterning of the dorsoventral axis of the limbs. In the kidneys the gene is predominantly expressed by podocytes, where it regulates the translation of many crucial genes, such as COL4A4, COL4A3, CD2AP, NPHS2, and NPHS1.

Clinical signs: Mutations of the LMX1B gene cause an autosomal dominant disorder called nail-patella syndrome, which involves skeletal abnormalities (dysplasia of the nails, patellar aplasia or hypoplasia, iliac horns, dysplasia of the elbows) and is often associated with hereditary glaucoma and progressive nephropathy.

Epidemiology: The incidence of the disease caused by LMX1B mutations is about 1 in 50,000 live births. The probability of new mutations seems to increase with father's age.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		9 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		6 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		9 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	Of the gene rearrangements, this method is useful to detect large deletions or duplications.

Literature: 

Browning MC et al. (1988) Renal histopathology of the nail-patella syndrome in a two-year-old boy.
Browning MC et al. (1988) Renal histopathology of the nail-patella syndrome in a two-year-old boy.
Dreyer SD et al. (1998) Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.
Vollrath D et al. (1998) Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.
McIntosh I et al. (1998) Mutation analysis of LMX1B gene in nail-patella syndrome patients.
Morello R et al. (2001) Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome.
Marini M et al. (2005) Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in Nail-Patella syndrome.
Hamlington JD et al. (2000) Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome.
Dunston JA et al. (2004) The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.
Bongers EM et al. (2005) Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy.
Lichter PR et al. (1997) Cosegregation of open-angle glaucoma and the nail-patella syndrome.
Bongers EM et al. (2002) Nail-patella syndrome. Overview on clinical and molecular findings.