Neurogenetics Reference Lab · Teaching Example
- Panel
- Ataxia Panel (185 genes)
- Report ID
- TEACH-0004
- Indication
- Progressive childhood-onset cerebellar ataxia, oculocutaneous telangiectasia, recurrent sinopulmonary infections.
- Specimen
- Peripheral blood, EDTA · Received 2026-01-30
- Reported
- 2026-02-12
- Methodology
- Targeted capture NGS, mean depth 240×. Splice predictions: SpliceAI, MaxEntScan. Parental segregation not yet performed.
Patient (anonymized teaching example)
Age 8 years · Female · Ashkenazi Jewish ancestry
Clinical: Progressive cerebellar ataxia onset age 3, ocular telangiectasias, elevated serum AFP, history of bacterial sinopulmonary infections. Family history of breast cancer (maternal aunt, age 42).
Reportable Variants
| Gene | Variant | Zygosity | Condition (Mode) | Origin | Classification |
|---|---|---|---|---|---|
Interpretation
This individual is heterozygous for the ATM variant c.5763-1G>A, which disrupts the () of intron 39. Splice predictors ( for acceptor loss) and the published literature support exon skipping or intron retention with consequent NMD. Loss-of-function is the established mechanism for ataxia-telangiectasia. The variant is absent from gnomAD. Classification: Pathogenic. Note: only one ATM pathogenic variant has been identified to date. For an autosomal-recessive diagnosis, a on the other allele is required. The clinical picture is highly consistent with A-T, so re-analysis for a second hit (deep intronic / large deletion / unannotated variant) is strongly recommended.
Recommendations
- •Genetic counseling for the family. Heterozygous ATM carriers have moderately elevated cancer risk (especially breast cancer in females); cascade testing of relatives is recommended.
- •Pursue a SECOND ATM hit: reflex deletion/duplication analysis (MLPA), deep intronic analysis from genome data if available, or RNA studies on a fresh sample.
- •Avoid ionizing radiation diagnostics (CT) where possible — A-T patients have profound radiosensitivity.
- •Tumor surveillance per A-T society guidelines (lymphoma/leukemia risk).
- •Immunology consultation for recurrent sinopulmonary infections.