Curation FAME4 YEATS2

Gene YEATS2

Disease FAME4

Inheritance AD

Score

3 + 3 = 6 / 18

Genetic + experimental = total

Classification

Limited

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 3

Publication Span 11 years

Publication Interval 11 years

Curator(s) Macayla Weiner, Laurel Hiatt, Elbay Aliyev

Description

Familial adult myoclonic epilepsy type 4 (FAME4) is an autosomal dominant disorder associated with intronic YEATS2 pentanucleotide repeat expansion/insertion. In a Thai BAFME4 family, long-read sequencing identified a YEATS2 intron 1 (TTTTA)n expansion with a TTTCA insertion, and RP-PCR/long-range PCR showed segregation of TTTCA insertions with disease in 13 affected relatives and absence from eight unaffected relatives and 1116 Thai controls. Earlier linkage mapped the disease locus to 3q26.32-q28. Gene-level Drosophila knockdown studies support a neuronal role for YEATS2.

All criTRia Curations Locus Page

Genetic evidence

Total: 3

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:31539032	1.5	One Thai BAFME4 family/proband: long-read sequencing identified an intronic YEATS2 (TTTTA)n expansion with TTTCA insertion; RP-PCR and long-range PCR confirmed expanded alleles in affected family members, with TTTCA absent from unaffected relatives and 1116 Thai controls.
Collective Evidence	Segregation	PMID:22713812	1.5	Genome-wide linkage in a Thai autosomal dominant BAFME family with 13 affected members mapped disease to chromosome 3q26.32-q28; D3S1262 had maximum two-point LOD 5.419 at θ=0, refined to a 10 Mb interval between D3S3730 and D3S1580.

Experimental evidence

Total: 3

Per page

Category	Type	Citation	Score	Details
Function	Biochemical function	PMID:38128822	0.5	Gene-level evidence: pan-neuronal dYEATS2 knockdown in Drosophila reduced dopamine content and lowered tyrosine hydroxylase transcript/protein levels, supporting a role for YEATS2 in dopamine biosynthesis; the human repeat expansion was not directly modeled.
Function	Regulatory impact	PMID:38128822	0.5	Gene-level expression evidence: dYEATS2 knockdown altered dopaminergic pathway expression markers, including reduced tyrosine hydroxylase and changes in vMAT/D2R; the study did not directly test regulatory effects of the human intronic TTTTA/TTTCA expansion.
Models	Non-human model organism	PMID:38128822	2	Drosophila pan-neuronal dYEATS2 knockdown caused seizure-like behaviours after electric, thermal, and mechanical stress, with locomotor/social/exploratory deficits; L-DOPA improved seizure-like and exploratory phenotypes. This models YEATS2 loss of function, not the human repeat expansion.

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