Muscular dystrophy and myopathy_Paediatric

Gene: COL12A1

I don't know

Additional infant proband but with limited clinical information, had chet canonical splice with a PTC.

VCGS patient: homozygous for a canonical splice variant with a severe neonatal presentation of arthrogryposis and muscular hypotonia.

Total: three reports, upgraded to green

Created: 27 Mar 2023, 12:56 a.m. | Last Modified: 27 Mar 2023, 5:34 a.m.

Panel Version: 0.128

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Ullrich congenital muscular dystrophy 2 MIM#616470

Publications

• 28973083
• 24334604

I don't know

Variants in this gene cause a rang of muscle disorders, only a single family reported with bi-allelic variants and a more severe, muscular dystrophy phenotype.

Created: 1 Jun 2022, 8:54 p.m. | Last Modified: 1 Jun 2022, 8:54 p.m.

Panel Version: 0.109

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ullrich congenital muscular dystrophy 2 , MIM# 616470

Publications

• 24334604

Green List (high evidence)

One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
18 cases from 12 unrelated families have been reported with monoallelic variants (both de novo and inherited), and one family has been reported with a homozygous variant. A null mouse model recapitulates the phenotype.

Created: 3 May 2022, 11:21 p.m. | Last Modified: 3 May 2022, 11:21 p.m.

Panel Version: 0.13647

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathic EDS; Bethlem myopathy 2 MIM#616471; Ullrich congenital muscular dystrophy 2 MIM#616470

Publications

• 28306229
• 31273343
• 24334604

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

Green List (high evidence)

Predominantly dominant inheritance reported, however a homozygous recessive loss of function variant which caused the most severe clinical phenotype, reminiscent of Ullrich disease but with clinically significant differences (PMID: 24334604). Both loss-of-function, resulting from premature termination codon (PMID: 24334604), and dominant negative, caused by glycine substitution (PMID: 24334769), have been reported.

Created: 12 Feb 2020, 3:38 a.m. | Last Modified: 12 Feb 2020, 3:38 a.m.

Panel Version: 0.19

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
?Ullrich congenital muscular dystrophy 2 616470 AR; Bethlem myopathy 2 616471 AD

Publications

• 24334604
• 24334769

Mode of pathogenicity
Other

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