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Fetal anomalies

Gene: DST

Green List (high evidence)
DST (dystonin)
EnsemblGeneIds (GRCh38): ENSG00000151914
EnsemblGeneIds (GRCh37): ENSG00000151914
OMIM: 113810, Gene2Phenotype
DST is in 11 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

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: 12 Dec 2025, 3:10 p.m. | Last Modified: 12 Dec 2025, 3:10 p.m.
Panel Version: 6.120
Created: 12 Dec 2025, 3:10 p.m.
Last Modified: 12 Dec 2025, 3:10 p.m.
Panel version: 6.120

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Additional reports of from cases with biallelic variants in the DST-b isoform which result in a distinct phenotype detectable neonatally in some cases:

PMID: 40497796 (2025) - biallelic variants in the DST impacting the DST-b isoform were identified in in 19 individuals from 14 unrelated families of different ethnicities by exome or genome sequencing or Sanger sequencing of affected siblings. Other likely pathogenic variants were excluded through sequencing analysis in line with ACMG classification guidelines.

8 variants were identified in these 19 patients with variants that only affect the DST-b isoform; 4 nonsense and 4 frameshift. All variants were absent or rare in gnomad. In 13 families the variant was homozygous and in 1 it was compound heterozygous.

Prenatal abnormalities were documented in 7/15 cases (reduced fetal movements and joint contractures). Of the 16 individuals assessed post birth, all displayed contractures at birth, 10/14 (from 9 families) displayed cardiomyopathy (9 with dilated cardiomyopathy), 14/14 (from 12 families) motor delay and 15/15 (from 12 families) muscular hypotonia.

RNA sequencing from control individuals showed that transcripts encoding DST-b isoform are expressed in skeletal muscle, heart tissue, and cultured fibroblasts. RNA sequencing analysis of patient fibroblasts from 3 affected individuals showed reduced DST RNA levels, but only in one case was this statistically signficant. However, proteomic studies with fibroblasts from 2 individuals showed a significant reduction of Dystonin, and a complete loss of the DST-b isoform. The author conclude this indicates that the DST-b transcripts escape NMD but encode a protein that is instable or rapidly degraded.

In addition, biallelic variants affecting both DST-a and DST-b isoforms were identified in 4 individuals from two families by exome sequencing. All presented with severe arthrogryposis and died intrauterine or shortly after birth.

PMID: 35942699 (2022) In a Dst-b-specific mutant mouse model with a nonsense mutation, the mice exhibit late-onset protein aggregate myopathy and cardiomyopathy without neuropathy.
Sources: Literature
Created: 2 Oct 2025, 12:29 p.m. | Last Modified: 2 Oct 2025, 12:29 p.m.
Panel Version: 6.90

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
arthrogryposis, MONDO:0859248; cardiomyopathy, MONDO:0004994; congenital myopathy, MONDO:0019952

Publications

Created: 2 Oct 2025, 12:29 p.m.
Last Modified: 2 Oct 2025, 12:29 p.m.
Panel version: 6.90

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

New gene added to this panel. There is sufficient evidence to make this gene Green at the next GMS panel update, inline with the recent review by the R21 Clinical Oversight Group.
Created: 5 Sep 2025, 4:41 p.m. | Last Modified: 5 Sep 2025, 4:41 p.m.
Panel Version: 6.29
Created: 5 Sep 2025, 4:41 p.m.
Last Modified: 5 Sep 2025, 4:41 p.m.
Panel version: 6.29

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

This gene and phenotype were reviewed during meetings in June & July 2025. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Elizabeth Scotchman (North Thames GLH), Natalie Bibb, Stephanie Allen & Sarah Graham (Central & South GLH) and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Elizabeth Wall, Sunayna Best, Soo-Mi Park & Sahar Mansour (R21 Clinical Oversight Group).
Created: 5 Sep 2025, 4:31 p.m. | Last Modified: 5 Sep 2025, 4:31 p.m.
Panel Version: 6.28
Three unrelated families with arthrogryposis multiplex congenita phenotype. One fetus from consanguineous Ashkenazi Jewish family with bilateral club feet and persistent clenching of the hands and homozygous frameshift variant; three infants from same family with same homozygous variants and distal contractures, dysautonomic symptoms and early death (22522446). Homozygous stop gain in a fetus with bilateral club feet and club hands with overlapping fingers and additional abnormalities on ultrasound; 3 newborns from 2 previous pregnancies of the couple had similar phenotype with perinatal lethality (35276021). Compound heterozygous stop gain and exon 25-96 deletion in a fetus with arthrogryposis multiplex congenita (37431644). NB Biallelic variants in DST also cause epidermolysis bullosa and HSAN depending on whether variants affect the epithelial or neuronal isoforms of DST.
Created: 5 Sep 2025, 2:55 p.m. | Last Modified: 5 Sep 2025, 2:55 p.m.
Panel Version: 6.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis multiplex congenita

Publications

Created: 5 Sep 2025, 2:55 p.m.
Last Modified: 5 Sep 2025, 2:55 p.m.
Panel version: 6.28

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
Phenotypes
  • Arthrogryposis multiplex congenita, MONDO:0015168
  • arthrogryposis, MONDO:0859248
  • cardiomyopathy, MONDO:0004994
  • congenital myopathy, MONDO:0019952
OMIM
113810
Clinvar variants
Variants in DST
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Dec 2025, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_25_promote_green was removed from gene: DST. Tag Q3_25_NHS_review was removed from gene: DST.

12 Dec 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Green was added to DST. Source NHS GMS was added to DST. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

2 Oct 2025, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: DST were set to 37431644; 40497796; 35942699

2 Oct 2025, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: DST were changed from Arthrogryposis multiplex congenita to Arthrogryposis multiplex congenita, MONDO:0015168; arthrogryposis, MONDO:0859248; cardiomyopathy, MONDO:0004994; congenital myopathy, MONDO:0019952

2 Oct 2025, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: DST were set to 37431644

8 Sep 2025, Gel status: 2

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: DST. Tag Q3_25_NHS_review tag was added to gene: DST.

5 Sep 2025, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: DST was added gene: DST was added to Fetal anomalies. Sources: Expert Review Amber Mode of inheritance for gene: DST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DST were set to 37431644 Phenotypes for gene: DST were set to Arthrogryposis multiplex congenita