Scientific background:

Summary: Mutations of the FH gene cause fumarase deficiency and hereditary leiomyomatosis and hereditary renal cancer often concurs.

Pathology: Fumarat hydratase is a key enzyme in Krebs cycle, which is respinsible for metabolism of tricarboxylic acids. The conversion of fumarate to malate is catalyzed.
Heterozygous mutations cause skin leiomyomatosis and these patients are of hight risk for renal-cell cancers.
Homozygous mutations are associated with early cerebral demage and growth failure.

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		Multiplex Ligation-Dependent Probe Amplification
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	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: 

Kim G et al. (2005) Multiple cutaneous and uterine leiomyomatosis (Reed's syndrome).
Alam NA et al. (2005) Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome.
Alam NA et al. (2005) Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer.
Kiuru M et al. (2004) Hereditary leiomyomatosis and renal cell cancer (HLRCC).
Pollard PJ et al. (2003) The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate dehydrogenase.