Arthrogryposis

Gene: MET

Green List (high evidence)

PMID:38429387 reported a second two-generation family with distal arthrogryposis and a MET variant (c.3704 A > G (p.Tyr1235Cys)), that was present in heterozygous state in both the mother and son.

Two unrelated cases and functional evidence are available in support of the disease association. Hence, this gene can be promoted to green rating.

Created: 7 Nov 2024, 10:52 a.m. | Last Modified: 7 Nov 2024, 10:52 a.m.

Panel Version: 0.414

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Arthrogryposis, distal, type 11, OMIM:620019

Publications

• 38429387

I don't know

Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad.

Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts.

Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.
Sources: Literature

Created: 1 Sep 2022, 6:29 a.m.

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

Phenotypes
?Arthrogryposis, distal, type 11 (MIM#620019), AD

Publications

• 30777867