Arthrogryposis

Gene: P4HA1

Red List (low evidence)

Comment on list classification: There is only 1 pedigree reported in literature where individuals harboured biallelic P4HA1 variants and presented with a connective tissue disorder. The symptoms had some overlap with EDS, including joint hypermobility, congenital hypotonia / muscle weakness, and contractures, but no evidence of vascular rupture or kyphoscoliosis. P4ha1 null mice are embryonic lethal. Based on available evidence, this gene should be rated Red, until more evidence emerges.

Created: 8 Jun 2026, 8:49 a.m. | Last Modified: 8 Jun 2026, 8:49 a.m.

Panel Version: 10.9

PMID: 28419360 Zou et al., 2017
Report of 2 sibs with early-onset joint hypermobility, joint contractures, muscle weakness, mild bone dysplasia, as well as high myopia. Biallelic P4HA1 mutations detected: c.1543 + 2 T > G (predicted to cause exon 12 skipping: p.Ala418_Arg434del) and c.1323_1324insAG, p.Arg362Glyfs*9. Seq method: WES. Variants confirmed in trans.
Muscle tissue from P1 and P2 was found to have reduced collagen IV immunoreactivity at the muscle basement membrane.

PMID: 17135260 Holster et al., 2007
P4ha1-/- null mice are embryonically lethal with evidence of impaired assembly of collagen IV at the basement membrane, whereas P4ha1+/- mice have no abnormalities
Sources: Literature

Created: 8 Jun 2026, 8:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
connective tissue disorder, MONDO:0003900

Publications

• 17135260
• 28419360