AUTOSOMAL DOMINANT PROGRESSIVE EXTERNAL OPTHALMOPLEGIA (ad-PEO 3)

TWINKLE/C10orf2 Sequencing

MITOCHONDRIAL DNA ANALYSIS

Also see: Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO) Panel


Twinkle is a nuclear-encoded mitochondrial DNA helicase. Dominant mutations of this mitochondrial DNA helicase cause adult-onset progressive external ophthalmoplegia (ad-PEO) with multiple mtDNA deletions. The disease manifests as myopathy, often affecting the extraocular, limb, and facial muscles, sometimes accompanied by major depression. In vitro, Twinkle has been shown to form a minimal mtDNA replisome together with the mitochondrial single-stranded DNA-binding protein and POLG. Twinkle is essential for mtDNA maintenance. Human cells devoid of Twinkle rapidly lose their mtDNA. The TWINKLE gene has 5 coding exons and is located on chromosome 10q24.

Reasons for Referral:

  • Confirmation of a clinical diagnosis
  • Carrier testing

Testing Methodology:

A PCR-based assay is used to amplify all exons and the immediately adjacent intronic regions of the TWINKLE gene. Direct sequence analysis of PCR products is performed in both the forward and reverse directions using automated fluorescent dideoxy sequencing methods.

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: 83904x10, 83898x5, 83912, 83891, 83894x2
Known Familial Mutation: 83904x4, 83912, 83898x2, 83891, 83894x2

Shipping Information


Forms:

>> Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included

References:

  1. Spelbrink JN et al. (2001) Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nat. Genet. 28: 223-231.
  2. Tyynismaa H et al. (2005) Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. PNAS 102: 17687-17692.
  3. Wanrooij W et al. (2004) Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA. NAR 32: 3053-3064.
  4. Deschauer M et al. (2003) A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia. Neuromuscular Disorders 13: 568-572.

Test Codes:

Index: 3175
Known Familial Mutation: 3176
Prenatal: 3177

Medical Genetics Laboratories
Baylor College of Medicine · Houston, TX 77030
Phone: 1-800-411-GENE · Fax: 713-798-2787
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