Congenital myopathy
Gene: ZC4H2
Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital) and others, variants in ZC4H2 cause a clinical phenotype that includes congenital arthrogryposis, joint contractures and muscle weakness similar to what has been seen in structural myopathies. As there is sufficient number of cases, this gene can be promoted to green at the next major review.Created: 26 Apr 2023, 11:34 a.m. | Last Modified: 26 Apr 2023, 11:56 a.m.
Panel Version: 4.27
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
as indicated also by other reviewers, variants in this gene cause a clinical phenotype that is in differential with classic congenital myopathy and affected individuals clearly have muscle weakness similar to what seen in patients with other structural myopathies. Similar genes like ECEL1 are already included in the panel.Created: 11 Feb 2023, 9:33 a.m. | Last Modified: 11 Feb 2023, 9:33 a.m.
Panel Version: 3.124
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mode of pathogenicity
Other
Comment on list classification: Changed from Green to Red. Updated rating from Anna Sarkozy as a result of GLH Test Group prior to sign offCreated: 3 Dec 2019, 2:50 p.m. | Last Modified: 3 Dec 2019, 2:50 p.m.
Panel Version: 1.198
Comment on mode of inheritance: MOI changed to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' as some female carriers also show signs of disease.Created: 18 Oct 2019, 11:34 a.m. | Last Modified: 18 Oct 2019, 11:34 a.m.
Panel Version: 1.183
After review with Genomics England clinical team this gene was deemed valid to include on the congenital myopathy panel, as affected individuals clearly have muscle weakness. The majority of boys with it have a level of severity that it is onset in utero, leading to contractures. Arthrogryposis and congenital myopathy are a clinical continuum and as long as the neuromuscular group do not disagree, so should on both panels.Created: 18 Oct 2019, 11:33 a.m. | Last Modified: 18 Oct 2019, 11:33 a.m.
Panel Version: 1.182
Comment on list classification: Changed rating from Red to Green based on recommendation from Guy's Hospital. Sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.Created: 17 Oct 2019, 9:41 a.m. | Last Modified: 17 Oct 2019, 9:41 a.m.
Panel Version: 1.173
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.
Tag Q2_23_NHS_review tag was added to gene: ZC4H2.
Tag Q2_23_promote_green tag was added to gene: ZC4H2.
Gene: zc4h2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ZC4H2 were changed from Wieacker-Wolff syndrome, 314580 to Wieacker-Wolff syndrome, OMIM:314580; Wieacker-Wolff syndrome, female-restricted, OMIM:301041
Gene: zc4h2 has been classified as Red List (Low Evidence).
Mode of inheritance for gene: ZC4H2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Gene: zc4h2 has been classified as Green List (High Evidence).
Publications for gene: ZC4H2 were set to 23623388, 26056227
Phenotypes for gene: ZC4H2 were changed from CAP myopathy 2, 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1, 108120; Arthrogryposis, distal, type 2B, 601680 to Wieacker-Wolff syndrome, 314580
Publications for gene: ZC4H2 were set to 12592607; 11738357; 17434307
Phenotypes for gene: ZC4H2 were changed from CAP myopathy 2, 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1 108120; Arthrogryposis, distal, type 2B 601680 to CAP myopathy 2, 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1, 108120; Arthrogryposis, distal, type 2B, 601680
Phenotypes for gene: ZC4H2 were changed from to CAP myopathy 2, 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1 108120; Arthrogryposis, distal, type 2B 601680
Publications for gene: ZC4H2 were set to
Mode of inheritance for gene: ZC4H2 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Source NHS GMS was added to ZC4H2.
gene: ZC4H2 was added gene: ZC4H2 was added to Congenital myopathy. Sources: London South GLH Mode of inheritance for gene: ZC4H2 was set to