Mutations in TIMM8A (Xq22) cause DDON. The TIMM8A gene encodes the mitochondrial import inner membrane translocase subunit Tim8 A protein and is involved in mitochondrial transport processes. DDON syndrome can also be part of a contiguous gene deletion syndrome at Xq22 which includes the TIMM8A and BTK genes and included X-linked agammaglobulinemia. The mutation detection rate is not yet known.
For patients with suspected DDON, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
- OMIM #300356: Translocase of Inner Mitochondrial Membrane 8.
- Confirmation of a clinical diagnosis of deafness-dystonia-optic neuronopathy syndrome in an individual in whom sequence analysis was negative.
- Carrier testing in adults with a family history of deafness-dystonia-optic neuronopathy syndrome in whom sequence analysis was negative.
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.
- Sequence analysis of the TIMM8A gene is available and is required before deletion/duplication analysis.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.