Fetal anomalies
Gene: AFF3

AFF3 (AF4/FMR2 family member 3)
EnsemblGeneIds (GRCh38): ENSG00000144218
EnsemblGeneIds (GRCh37): ENSG00000144218
OMIM: 601464, Gene2Phenotype
AFF3 is in 9 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

16 affected individuals reported with de novo missense variants. All variants occurred within the degron motif of the ALF domain. The highly conserved 9-amino acid motif mediates the interaction with SIAH E3 ubiquitin ligases and regulates their degradation. Thirteen of the probands carried variants affecting the same codon in exon 6, ala258.

All probands presented with severe developmental epileptic encephalopathy along with mesomelic dysplasia (12/18) and failure to thrive (14/18). The skeletal features included short forearms, radial head dislocation/subluxation, triangular and/or short tibia, fibular hypoplasia, hip dislocation, and tarsal and/or metatarsal synostosis resembling Nievergelt/Savarirayan mesomelic skeletal dysplasia. Other features included microcephaly (9/18), global brain atrophy and/or ventriculomegaly (13/15), fibular hypoplasia (12/16), horseshoe or hypoplastic kidney (13/17), abnormalities of muscle tone (12/16), gastroesophageal reflux disease (6/16), and other gastrointestinal symptoms (14/17). The patients also shared common dysmorphic facial features such as a bulbous nasal tip (10/15), a wide mouth (10/16) often with a square upper lip, abnormalities of the teeth and gums (12/15), and hypertrichosis (12/15). The constellation of features recalled some features of CHOPS syndrome, which is caused by mutations in a related gene, AFF4.
Created: 12 May 2021, 9:22 a.m. | Last Modified: 12 May 2021, 9:22 a.m.

Panel Version: 0.3758

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
KINSSHIP syndrome, MIM# 619297

Publications

Created: 12 May 2021, 9:22 a.m.
Last Modified: 12 May 2021, 9:22 a.m.
Panel version: Imported from Intellectual disability syndromic and non-syndromic panel version 0.3758

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Genomics England PanelApp
Genetic Health Queensland

Phenotypes

KINSSHIP syndrome, MIM# 619297

OMIM

601464

Clinvar variants

Variants in AFF3

Penetrance

None

Publications

Panels with this gene