Neurogenetics Reference Lab · Teaching Example
- Panel
- Mitochondrial DNA full sequencing + heteroplasmy quantification
- Report ID
- TEACH-0012
- Indication
- Diabetes mellitus + sensorineural hearing loss + brief stroke-like episodes; suspected MELAS/MIDD.
- Specimen
- Peripheral blood, EDTA · Received 2026-03-25
- Reported
- 2026-04-09
- Methodology
- Whole mtDNA sequencing by deep NGS (mean depth 12,000×) with heteroplasmy quantification down to ~1%. Confirmation on a urine sample recommended.
Patient (anonymized teaching example)
Age 34 years · Female · Mixed ancestry
Clinical: Type 2 diabetes at age 30 (no insulin resistance features). Bilateral sensorineural hearing loss progressive since mid-20s. Two episodes of transient hemiparesis with cortical MRI signal change. Mother had diabetes; maternal grandmother had hearing loss.
Reportable Variants
| Gene | Variant | Zygosity | Heteroplasmy | Condition (Mode) | Origin | Classification |
|---|---|---|---|---|---|---|
| 28% (blood) |
Interpretation
The well-established pathogenic m.3243A>G (in the MT-TL1 gene) was detected at . This is the most common pathogenic mtDNA variant, causing a clinical spectrum from maternally-inherited diabetes and deafness (MIDD) to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient's phenotype (diabetes + sensorineural hearing loss + brief stroke-like episodes) is highly consistent with the MIDD/MELAS spectrum. the level in affected tissues — urine, buccal swab, or muscle generally show higher percentages and are more clinically informative. .
Recommendations
- •Confirm heteroplasmy on urine and/or buccal swab; muscle biopsy if clinically indicated. Blood heteroplasmy alone underestimates tissue burden.
- •Multidisciplinary mitochondrial care: endocrinology (diabetes management — avoid metformin given lactic acidosis risk), audiology, cardiology, ophthalmology.
- •Avoid mitochondrial toxins: aminoglycosides, valproate, linezolid.
- •Maternal family cascade testing: ALL maternal relatives are at risk and should be offered testing.
- •Reproductive counseling — affected women can transmit at unpredictable levels (mitochondrial bottleneck). Discuss reproductive options including mitochondrial replacement, oocyte donation, or PGT (with caveats about its limitations for mtDNA disorders).