Arthrogryposis

Gene: USP14

I don't know

Comment on list classification: There is currently one family reported with three foetuses with distal arthrogryposis and biallelic USP14 variants. There is also evidence available from mouse model showing congenital contractures. Hence, this gene can be rated amber with the current evidence.

Created: 6 Nov 2026, 10:14 a.m. | Last Modified: 6 Nov 2026, 10:14 a.m.

Panel Version: 10.31

PMID:35066879 reported the identification of a biallelic 4-bp deletion variant (p.Leu78Glnfs*11) in USP14 gene in three foetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Usp14-deficient mice showed a phenotype similar to lethal human multiple congenital contractures phenotype, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool.

PMID:38469793 reported the identification of biallelic variants in four cases (one foetus, a newborn with a syndromic neurodevelopmental disorder and two siblings with a progressive neurological disease) from three unrelated families. The two siblings had compound heterozygous variants (p.Leu3Pro and p.Arg330Ter), whereas both foetus ( p.Lys300Serfs∗24) and newborn (p.Leu78Glnfs∗11) harboured different homozygous variants.

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature

Created: 6 Nov 2026, 10:12 a.m. | Last Modified: 6 Nov 2026, 10:26 a.m.

Panel Version: 10.31

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
syndromic disease, MONDO:0002254; distal arthrogryposis, MONDO:0019942

Publications

• 35066879
• 38469793