BCS1L RELATED COMPLEX III DEFICIENCY
BCS1L Sequencing
MITOCHONDRIAL DNA ANALYSIS

Description:

Complex III (CIII, ubiquinol cytochrome c reductase of the mitochondrial respiratory chain) consists of 11 protein subunits, of which all but one (cytochrome b) are encoded by the nuclear genome. Mutation analysis of the 10 structural nuclear CIII genes has not been performed. BCS-1L is the only identified nuclear gene which may play a role in complex III assembly, and is involved either in forming the active site iron-sulfur cluster or in providing a chaperone-like function in assembling the iron-sulfur proteins with other subunits of the complex. Mutations in BCS-1L have been reported in patients presenting with neonatal proximal tubulopathy, liver failure, and encephalopathy. More recently, BCS-1L mutations have been identified in Finnish patients with a lethal metabolic disorder with iron overload, GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death) syndrome. In this disorder, complex III activity was within the normal range, implying that BCS1L has a cellular function that is essential in iron metabolism.

Reasons for Referral:

To confirm a clinical diagnosis of affected individuals.

Testing Methodology:

The exons and flanking intron regions of BCS-1L gene are PCR amplified and sequenced.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83904x8, 83898x4, 83912, 83891, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
>> Prenatal Requisition

References:

1.de Lonlay P, Valnot I, Barrientos A, Gorbatyuk M, Tzagoloff A, Taanman JW, Benayoun E, Chretien D, Kadhom N, Lombes A, de Baulny HO, Niaudet P, Munnich A, Rustin P, Rotig A. (2001) A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure. Nat. Genet. 29: 57-60.
2. Visapaa I, Fellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V, Payne GS, Makarow M, Van Coster R, Taylor RW, Turnbull DM, Suomalainen A, Peltonen L. (2002) GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L. Am. J. Hum. Genet. 71: 863-876.

Test Codes:

Index: 3110
Known Familial Mutation: 3111
Prenatal: 3112