Arthrogryposis
Gene: KIF21A
The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 4:08 p.m. | Last Modified: 10 Oct 2023, 4:08 p.m.
Panel Version: 5.15
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on classification: There is sufficient evidence to recommend this gene to NHS GMS for promoting to green rating.
There are two unrelated families with homozygous loss of function variants in KIF21A were reported with severe fetal akinesia with arthrogryposis multiplex in PMID:34740919. Hannah Robinson (South West Genomic Laboratory Hub) reported an additional case identified in Exeter Genomics Laboratory exhibiting homozygous nonsense variant in KIF21A and was diagnosed with arthrogryposis.
In addition, PMID:32686171 reports overlapping phenotypes observed in KIF21A null piglets, where a 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita.Created: 7 Feb 2023, 5:34 p.m. | Last Modified: 7 Feb 2023, 5:34 p.m.
Panel Version: 4.5
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
arthrogryposis, MONDO:0008779; fetal akinesia
Publications
Falb et al 2023 (PMID: 34740919) describe two unrelated families in which biallelic loss of function variants segregated with a severe form of fetal akinesia characterised by arthrogryposis multiplex, pulmonary hypoplasia and variable facial dysmorphisms.
Exeter Genomics Laboratory has identified an unrelated third case homozygous for a nonsense variant in KIF21A. The patient had an antenatal diagnosis of talipes, arthrogryposis, polyhydramnios and lack of fetal movements. At birth, all joints displayed fixed flexion deformities, no primitive reflexes, poor muscle bulk and care was re-oriented shortly after birth.
Taken together, three unrelated cases including segregation evidence in the published families provides sufficient evidence for the gene-disease association.
Sources: Literature, NHS GMSCreated: 18 Jan 2023, 8:49 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Arthrogryposis; fetal akinesia
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q1_23_promote_green was removed from gene: KIF21A. Tag Q1_23_NHS_review was removed from gene: KIF21A.
Source Expert Review Green was added to KIF21A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q1_23_NHS_review tag was added to gene: KIF21A.
Phenotypes for gene: KIF21A were changed from Arthrogryposis; fetal akinesia to arthrogryposis, MONDO:0008779; fetal akinesia
Publications for gene: KIF21A were set to 34740919
Gene: kif21a has been classified as Amber List (Moderate Evidence).
Tag Q1_23_promote_green tag was added to gene: KIF21A.
gene: KIF21A was added gene: KIF21A was added to Arthrogryposis. Sources: Literature,NHS GMS Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF21A were set to 34740919 Phenotypes for gene: KIF21A were set to Arthrogryposis; fetal akinesia Penetrance for gene: KIF21A were set to unknown Review for gene: KIF21A was set to GREEN gene: KIF21A was marked as current diagnostic