Curation FAME2 STARD7

Gene STARD7

Disease FAME2

Inheritance AD

Score

12 + 0 = 12 / 18

Genetic + experimental = total

Classification

Strong

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 1

Publication Span –

Publication Interval –

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 12

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.