Congenital muscular dystrophy and congenital myopathy

Gene: TPM2

Green List (high evidence)

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 4:01 p.m.

Panel Version: 0.229

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.

Created: 24 Dec 2023, 10:46 p.m. | Last Modified: 24 Dec 2023, 10:46 p.m.

Panel Version: 0.217

PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.

Created: 24 Dec 2023, 10:44 p.m. | Last Modified: 24 Dec 2023, 10:44 p.m.

Panel Version: 0.216

Anna Sarkozy (Great Ormond Street Hospital) editing her previous review on this gene on the old GMS Congenital myopathy panel on 24 Mar 2023 notes (rated Green): 'comment re inheritance: recessive TPM2 pathogenic variant has been described in a patient with multiple pterygium syndrome and congenital myopathy. heterozygous carrier parents were unaffected, supporting recessive inheritance of the variant.'

Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes: CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy

Publications: 33558124

Created: 24 Dec 2023, 10:37 p.m. | Last Modified: 24 Dec 2023, 10:37 p.m.

Panel Version: 0.216

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 19155175
• 24692096
• 33558124

As there are only currently 2 homozygous cases, there is currently not enough evidence to support a change in MOI. It should also be noted that the parents (heterozygous for the variants) were asymptomatic.

Created: 12 Jul 2021, 10:43 a.m. | Last Modified: 12 Jul 2021, 10:43 a.m.

Panel Version: 2.55

Comment on publications: PMID: 19155175 and 33558124 describe the 2 homozygous cases

Created: 12 Jul 2021, 9:50 a.m. | Last Modified: 12 Jul 2021, 9:50 a.m.

Panel Version: 2.53

Green List (high evidence)

Note two families reported now with bi-allelic disease, one presenting with congenital myopathy and the other with multiple pterygium syndrome.

Created: 13 Jun 2021, 7:58 a.m. | Last Modified: 13 Jun 2021, 7:58 a.m.

Panel Version: 2.28

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy; Multiple pterygium syndrome

Publications

• 32092148
• 27726070

I don't know

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
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1 108120: Arthrogryposis, distal, type 2B 601680

Publications

• 12592607, 11738357, 17434307

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

Green List (high evidence)

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

Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285

Green List (high evidence)

Comment when marking as ready: Many families, monoallelic except single case with pterygia

Created: 2 Feb 2017, 12:10 p.m.

Comment on mode of inheritance: One case of Nemaline myopathy and pterygia found with homozygous mutation. All heterozygous otherwise.

Created: 2 Feb 2017, 12:09 p.m.

Note that the only cases I found of truncating mutations were in a homozygous form. Otherwise, dominant inheritance appears to be associated with missense mutations.

Created: 26 Jan 2017, 1:12 p.m.

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

Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285

Publications

• PMID 24692096