Arthrogryposis

Gene: TTN

Green List (high evidence)

By Sanger sequencing the TTN gene in 31 patients from 23 families segregating congenital core myopathy and primary heart disease, Chauveau et al. (2014) identified homozygous or compound heterozygous mutations in 5 patients from 4 families. The severity of the phenotype varied among the families. All 5 patients had congenital or infantile muscle weakness with axial and distal joint contractures and relatively preserved respiratory function. One individual presented with arthrogryposis, dislocated hips with dysplasia, and elbow, hip, and knee contractures.
Bryen et al: eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (c.39974-11T>G), inherited in trans with a second pathogenic TTN variant.
Two families with AMC and biallelic truncating mutations in 29575618; 28040389.

Created: 27 Nov 2019, 12:35 p.m. | Last Modified: 28 Nov 2019, 4:30 p.m.

Panel Version: 2.101

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10

Publications

• PubMed: 24105469
• 31660661
• 29575618
• 28040389

Comment on mode of inheritance: With agreement from Zerin Hyder, changed MOI from 'BOTH monoallelic and biallelic' to 'BIALLELIC' to match MOI on 'Neuromuscular arthrogryposis' panel V0.21 and review on DDG2P panel by Lucy Raymond.

Created: 26 Nov 2019, 1:19 p.m. | Last Modified: 29 Nov 2019, 12:57 p.m.

Panel Version: 2.101

Upgraded TTN from Red to Green. TTN was reviewed on the DDG2P panel by Lucy Raymond with the comment: "Biallelic LOF are congenital titinopathy with arthrogryposis". There is a second case from 2017 (PMID:28040389) and 8 more families in PMID:31660661. TTN is also Green on the 'Neuromuscular arthrogryposis' panel V0.21.

Created: 26 Nov 2019, 1:15 p.m. | Last Modified: 26 Nov 2019, 1:15 p.m.

Panel Version: 2.47

Red List (low evidence)

Arthrogryposis only reported in one patients with biallelic TTN mutations

Created: 22 Dec 2016, 2:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
core myopathy with heart disease

Publications

• 24105469