Skeletal dysplasia

Gene: COL27A1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 6:08 p.m. | Last Modified: 24 Feb 2025, 6:08 p.m.

Panel Version: 7.23

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 17 Jul 2024, 5:53 p.m. | Last Modified: 17 Jul 2024, 5:53 p.m.

Panel Version: 5.8

PMID:24986830 reported the identification of a homozygous missense variant in COL27A1 gene (p.Gly697Arg) in a non-consanguineous family of Hispanic Puerto Rican descent with Steel syndrome. The sibling pair presented with bilateral congenital hip dysplasia and coxa vara. The identified variant seems to have arisen as a founder mutation in the Puerto Rican population.

PMID:28276056 reported a 5-year-old girl from a non-consanguineous family of Indian descent with facial dysmorphism, short stature, carpal coalition, dislocation of radial heads, bilateral hip dislocation, scoliosis and vertical talus. This patient also had developmental delay and hearing loss and was identified with novel compound heterozygous variants c.521_528del (p.Cys174Serfs*34) and c.2119C>T (p.Arg707Ter) in COL27A1.

PMID:28322503 reported a child from a consanguineous family of Emirati descent with features of Steel syndrome, including bilateral hip dislocations, short upper limbs, and dysmorphic facial features. She had delayed speech and severe bilateral sensorineural hearing loss. She was identified with a novel homozygous splice site variant in COL27A1 (c.3556-2A>G).

PMID:31903681 reported three more patients of Puerto Rican descent with Steel syndrome and with the previously reported founder variant (p.Gly697Arg). They had either hip dislocations or hip dysplasia.

PMID:32360765 reported a 4-year-old boy from a non-consanguineous family of European descent with dysmorphic facial features, absent hip ossification centres, external rotation of both feet, relatively short stature, mild skin syndactyly, short mid phalanges and bilateral sensorineural hearing loss. He was identified with a novel homozygous missense variant p.(Gly802Glu) in COL27A1.

PMID:33963180 reported the identification of novel compound heterozygous variants (c.4229_4233dup/ p.Gly1412Argfs*157 and c.3718_5436del/ p.Gly1240_Lys1812del) in COL27A1 in an 11-year-old child from a non-consanguineous family of Korean descent. He presented with short stature, hip dysplasia, radial head dislocation, carpal coalition, genu valgum, and fixed patellar dislocation and was clinically diagnosed with Steel syndrome.

This gene has been associated with relevant phenotypes in OMIM (MIM #615155) and Gene2Phenotype (with 'definitive' rating on the DD panel).
Sources: Literature

Created: 17 Jul 2024, 5:52 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Steel syndrome, OMIM:615155

Publications

• 24986830
• 28276056
• 28322503
• 31903681
• 32360765
• 33963180