Congenital myopathy

Gene: TRIP4

Green List (high evidence)

TRIP4 (thyroid hormone receptor interactor 4)
EnsemblGeneIds (GRCh38): ENSG00000103671
EnsemblGeneIds (GRCh37): ENSG00000103671
OMIM: 604501, Gene2Phenotype
TRIP4 is in 8 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: After review, it was agreed that it was an appropriate phenotype, sufficient cases to support gene-disease association. The gene is also Green on Neuromuscular disorders
Created: 9 Oct 2019, 12:38 p.m. | Last Modified: 9 Oct 2019, 12:38 p.m.
Panel Version: 1.165
Reviewed by Ivone Leong (Genomics England Curator)
PMID: 26924529 reported on 3 families (2 Kosovo and 1 Albania) who have 2 different variants in TRIP4. The affected individuals presented with prenatal-onset SMA, multiple congenital contractures (arthrogryposis multiplex congenita), respiratory distress, and congenital bone fractures. The authors suspect a founder effect in the Kosovo families. I think I would count this as 2 cases because of this.
There is another paper (PMID: 27008887) which reported on a large family with TRIP4 variant who have neonatal hypotonia particularly marked in axial (neck and trunk) muscles, severe head lag, poor antigravity limb movements and in some patients, respiratory failure and feeding difficulties. There were no congenital contractures. OMIM has classified this variant as Davignon-Chauveau-type congenital muscular dystrophy. Could this be counted as a third case?

Genomics England clinical team noted there was sufficient for a green rating. The fact that a second case has been found, besides the potential founder variant, and there is a supportive animal model would meet our criteria. additional paper adds evidence of a neuromuscular phenotype associated with this gene

The GLH representative has rated it green so would support green rating. The panel has not yet been discussed with the Test Group, but all genes will be reviewed before sign off.
Created: 9 Oct 2019, 12:35 p.m. | Last Modified: 9 Oct 2019, 1:35 p.m.
Panel Version: 1.166
Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.
Created: 30 Apr 2019, 10:09 a.m.

Rachael Mein (Viapath at Guy's Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe congenital myopathy with congenital bone fractures 616866

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • London South GLH
Phenotypes
  • Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866
  • Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209
  • Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806
  • ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066
  • Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896
OMIM
604501
Clinvar variants
Variants in TRIP4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

4 Jan 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TRIP4 were changed from severe congenital myopathy with congenital bone fractures, 616866; Spinal muscular atrophy with congenital bone fractures 1, 616866 to Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806; ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896

9 Oct 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: trip4 has been classified as Green List (High Evidence).

9 Oct 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: TRIP4 were set to 26924529

8 Aug 2019, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: TRIP4 were changed from severe congenital myopathy with congenital bone fractures, 616866 to severe congenital myopathy with congenital bone fractures, 616866; Spinal muscular atrophy with congenital bone fractures 1, 616866

3 May 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TRIP4 were changed from vacuolar myopathy? to severe congenital myopathy with congenital bone fractures, 616866

3 May 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: TRIP4 were set to 23315026

30 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TRIP4 were changed from to vacuolar myopathy?

30 Apr 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: TRIP4 were set to

30 Apr 2019, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: TRIP4 was changed from to BIALLELIC, autosomal or pseudoautosomal

30 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TRIP4.

30 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: TRIP4 was added gene: TRIP4 was added to Congenital myopathy. Sources: London South GLH Mode of inheritance for gene: TRIP4 was set to