Arthrogryposis

Gene: SYNE1

The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.

Created: 11 Mar 2022, 1:41 p.m. | Last Modified: 11 Mar 2022, 1:41 p.m.

Panel Version: 3.154

Green List (high evidence)

Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote to Green at the next GMS panel update.

Created: 8 Feb 2021, 2:59 p.m. | Last Modified: 8 Feb 2021, 2:59 p.m.

Panel Version: 3.70

Associated with relevant phenotype in OMIM (MIM# 618484) but not yet in Gene2Phenotype.

At least 3 unrelated families with AMC, characterised by decreased fetal movements, hypotonia, skeletal defects, and delayed motor milestones with difficulty walking. Different homozygous truncating variants in SYNE1 were detected, which lead to loss of the KASH domain (PMIDs: 19542096; 24319099; 27782104)

All affecteds lacked pyramidal or cerebellar involvement, highlighting that this represents a distinct disorder from the cerebellar ataxia phenotype also associated with biallelic variants in this gene.

Created: 8 Feb 2021, 2:57 p.m. | Last Modified: 8 Feb 2021, 2:57 p.m.

Panel Version: 3.69

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484; Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778

Publications

• 19542096
• 24319099
• 27782104

Green List (high evidence)

Three families reported with bi-allelic distal truncating variants in this gene (KASH domain). This appears to be a specific genotype-phenotype correlation with variants elsewhere in the gene causing different phenotypes.

Created: 12 Jul 2020, 11:02 a.m. | Last Modified: 12 Jul 2020, 11:02 a.m.

Panel Version: 3.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Distal arthrogryposis

Publications

• 27782104

Variants in this GENE are reported as part of current diagnostic practice

Comment when marking as ready: Arthrogryposis only reported in one family with SYNE1

Created: 22 Dec 2016, 3:06 p.m.

I don't know

causes variety of neuromuscular presentations whilst these are not the more classic CMD there is a wide phenotypic spectrum (AD/ AR inheritance cerebellar ataxia or hypotonia and contratcures). Could make a case for this being a green gene.

Created: 19 Dec 2016, 11:47 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Emery-Dreifuss Muscular Dystrophy; Spinocerebellar ataxia, autosomal recessive 8, 610743