PUBLICATION
A Novel Variant in AFF3 Underlying Isolated Syndactyly
- Authors
- Khan, H., Koh, G., Chong, A.E.Q., Zahid, M., Hussain, S., Ali, H., Ahmad, W., Xue, S.
- ID
- ZDB-PUB-221025-1
- Date
- 2022
- Source
- Clinical genetics 103(3): 341-345 (Journal)
- Registered Authors
- Xue, Shifeng
- Keywords
- AFF3, Exome Sequencing, Isolated Syndactyly, Rare Disease
- MeSH Terms
-
- Animals
- Humans
- Limb Deformities, Congenital*/genetics
- Mutation, Missense
- Nuclear Proteins/genetics
- Pedigree
- Syndactyly*/genetics
- Transcription Factors/genetics
- Zebrafish/genetics
- PubMed
- 36273379 Full text @ Clin. Genet.
Citation
Khan, H., Koh, G., Chong, A.E.Q., Zahid, M., Hussain, S., Ali, H., Ahmad, W., Xue, S. (2022) A Novel Variant in AFF3 Underlying Isolated Syndactyly. Clinical genetics. 103(3):341-345.
Abstract
Isolated syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover a novel heterozygous missense variant c.2915G>C: p.Arg972Pro in AFF3 on chromosome 2q11.2 in a family with isolated syndactyly in hands and feet. AFF3 belongs to a family of nuclear transcription activating factors and is involved in limb dorsoventral patterning. The variant Arg972Pro is located near the C terminus, a region that is yet to be associated with human disorders. Functional studies did not show a difference in the stability or subcellular localization of the mutant and wild type proteins. Instead, overexpression in zebrafish embryos suggests that Arg972Pro is a loss-of-function allele. These results suggest that variants in the C terminus of AFF3 may cause a phenotype distinct from previously characterized AFF3 variants.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping