FRA2A AFF3

Disease ID
FRA2A
Gene ID
AFF3
Clinical Links
MalaCard
KNS007
OMIM
601464
Bioinformatical Links
TR-Atlas
TR252468
WebSTR hg38
288936

Disease

Name
Intellectual disability associated with fragile site FRA2A
Inheritance
Autosomal dominant
Description
These expansions are associated with intellectual disability and clinical phenotypes such as delayed motor development or delays in speech/language1 .
Prevalence
1/862 (1/654-1266) population prevalence of methylated AFF3 expansions (mild cognitive disability)2 . Disease cases observed in South Australia1 .
Age of OnsetYears1  7
Age of Onset Details
Early childhood (small sample size)1 .

Locus

hg19
chr2:100721261-100721286
hg38
chr2:100104799-100104824
t2t
chr2:100563686-100563738
Details
Allele ranges established in study of 3 families; intermediate alleles likely premutations1 . Pathogenic threshold may be higher than 300 as this was the largest allele that could be accurately sized by the assay.
Mechanism
LoF/methylation
Silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene3 .
Year
20141
Location in Gene
Intron 3
Gene Strand

Alleles

Ref. Motif
GCC
Pathogenic (ref.)
GCC
Pathogenic (gene)
CGG
BenignPathogenicUnits3  20300  300

References

Direct supporting references for info on this page.

1
FRA2A is a CGG repeat expansion associated with silencing of AFF3.
Sofie,Metsu, Liesbeth,Rooms, Jacqueline,Rainger, Martin S,Taylor, Hemant,Bengani, David I,Wilson, Chandra Sekhar Reddy,Chilamakuri, Harris,Morrison, Geert,Vandeweyer, Edwin,Reyniers, Evelyn,Douglas, Geoffrey,Thompson, Eric,Haan, Jozef,Gecz, David R,Fitzpatrick, R Frank,Kooy
PLoS genetics · 2014-04-24
pmid:24763282
2
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in<i>AFF3</i>as a significant cause of intellectual disability
Bharati,Jadhav, Paras,Garg, Joke J. F. A.,van Vugt, Kristina,Ibanez, Delia,Gagliardi, William,Lee, Mariya,Shadrina, Tom,Mokveld, Egor,Dolzhenko, Alejandro,Martin-Trujillo, Scott L.,Gies, Clarissa,Rocca, Mafalda,Barbosa, Miten,Jain, Nayana,Lahiri, Katherine,Lachlan, Henry,Houlden, Benedict,Paten, Jan,Veldink, Arianna,Tucci, Andrew J.,Sharp
Cold Spring Harbor Laboratory · 2023-05-05
doi:10.1101/2023.05.03.23289461
3
malacard:KNS007

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.
Bharati,Jadhav, Paras,Garg, Joke J F A,van Vugt, Kristina,Ibanez, Delia,Gagliardi, William,Lee, Mariya,Shadrina, Tom,Mokveld, Egor,Dolzhenko, Alejandro,Martin-Trujillo, Scott J,Gies, Gabrielle,Altman, Clarissa,Rocca, Mafalda,Barbosa, Miten,Jain, Nayana,Lahiri, Katherine,Lachlan, Henry,Houlden, Benedict,Paten, Jan,Veldink, Arianna,Tucci, Andrew J,Sharp
Nature genetics · 2024-09-23
pmid:39313615