FAME2_STARD7
- Gene
- STARD7
- Disease
- FAME2
- Inheritance
- AD
- Classification
- Strong
- Total Score
- 12
- Publications Reviewed
- 1
- Publication Span
- Last Updated
- 08/14/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
FAME2 is caused by an intronic ATTTC pentanucleotide repeat expansion in the first intron of STARD7. Corbett et al. identified ATTTT/ATTTC repeat expansions in the chromosome 2 FAME interval using WGS-based ExpansionHunter/exSTRa analysis and validated the STARD7 ATTTC expansion by repeat-primed PCR. The expansion segregated with FAME in 158 affected individuals from 22 pedigrees and was absent from tested controls; anticipation was observed in a large family, while STARD7 mRNA and protein abundance were not altered in available patient-derived fibroblasts, supporting a repeat-sequence mechanism rather than STARD7 loss of expression.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:31664034 | 6 | Twenty-two FAME2 pedigrees were investigated; 158 affected individuals tested positive for the intronic STARD7 ATTTC expansion by RP-PCR, including 137/137 affected individuals from 16 previously reported chromosome 2-linked families and 20/20 familial clinically similar cases. |
| Collective Evidence | Allele | PMID:31664034 | 1 | Long-read sequencing resolved expanded STARD7 repeat structures in affected individuals, including combined AAATG/AAAAT insertions of ~3.3–4.6 kb, and Family 1 showed anticipation with median onset decreasing from generation III (30 years) to IV (17 years) to V (12 years). |
| Collective Evidence | Computational | PMID:31664034 | 0.5 | Short-read WGS analysis with ExpansionHunter and exSTRa identified ATTTT/ATTTC repeat expansions in the FAME2 interval in affected samples; all FAME2 carriers were significant exSTRa outliers at the FAME2-AAATG locus (p < 0.0001) compared with 69 unaffected WGS controls. |
| Collective Evidence | Segregation | PMID:31664034 | 1.5 | RP-PCR showed the STARD7 ATTTC expansion segregated with FAME in 158/158 affected individuals across 22 families; 24 unaffected relatives were negative, and two expansion-positive individuals without a FAME diagnosis were from younger generations and considered likely presymptomatic. |
| Statistics | Case-control data | PMID:31664034 | 6 | The ATTTC repeat was absent from WGS data for 69 controls and did not amplify in 28 unaffected unrelated control DNA samples; among family testing, 158 affected individuals were expansion-positive and no affected individuals were expansion-negative. |
Experimental evidence
Total: 0
No experimental evidence details available.
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.