Arthrogryposis

Gene: SLC18A3

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 12:24 p.m. | Last Modified: 26 Sep 2024, 12:24 p.m.

Panel Version: 7.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: As reviewed by Hannah Knight, PMID:34943989 reports an additional patient with compound heterozygous variants in SLC18A3 gene and presenting with arthrogryposis congenital (AMC). Hence, there is sufficient evidence available for promoting this gene to green rating in the next GMS review.

Created: 24 Apr 2024, 5:12 p.m. | Last Modified: 24 Apr 2024, 5:12 p.m.

Panel Version: 5.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239; arthrogryposis, MONDO:0008779

Green List (high evidence)

PMID: 34943989 report a new case in a child with contractures, among other features. One nonsense variant, one missense variant. They suggest a more severe phenotype to those previously reported "possibly related to a more severe effect of the nonsense variant"

Created: 17 Apr 2024, 2:06 p.m. | Last Modified: 17 Apr 2024, 2:06 p.m.

Panel Version: 5.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 21, presynaptic

Publications

• PMID: 34943989

Comment on list classification: Kept rating as Amber on advice from Zerin Hyder (Genomics England clinical team): 2 families with strong link to arthrogryposis.

Created: 28 Nov 2019, 4:21 p.m. | Last Modified: 28 Nov 2019, 4:21 p.m.

Panel Version: 2.101

Comment on publications: PMID:27590285: report individuals from 2 families with biallelic SLC18A3 variants and presynaptic congenital myasthenic syndrome.

Created: 28 Nov 2019, 3:52 p.m. | Last Modified: 28 Nov 2019, 3:52 p.m.

Panel Version: 2.98

PMID:28188302 (Aran et al., 2017) report 2 brothers from a nonconsanguineous Yemeni Jewish family manifested at birth with severe hypotonia and arthrogryposis. The brothers were homozygous for missense variant in SLC18A3 c.1078G>C, p.Gly360Arg.

Created: 28 Nov 2019, 3:50 p.m. | Last Modified: 28 Nov 2019, 3:50 p.m.

Panel Version: 2.97

PMID:31059209 (Hakonen et al., 2019) report 2 sibling Finnish fetuses with with fetal akinesia, arthrogryposis, edema, and partial cleft palate and a homozygous variant in SLC18A3: c.1116C>A, p.(Cys372Ter). The parents were distant relatives.

Created: 28 Nov 2019, 3:50 p.m. | Last Modified: 28 Nov 2019, 3:50 p.m.

Panel Version: 2.97

Added to panel based on Amber rating on Neuromuscular arthrogryposis panel V0.21 and literature evidence supporting an Arthrogryposis phenotype.
Sources: Other, Literature

Created: 28 Nov 2019, 3:48 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis

Publications

• 28188302
• 27590285
• 31059209