Congenital muscular dystrophy and congenital myopathy

Gene: TRIP4

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.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe congenital myopathy with congenital bone fractures 616866

Publications

• 26924529

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