COL27A1 gene

The COL27A1 gene (collagen type XXVII alpha 1 chain) is a protein coding gene located on chromosome 9q32.

The COL27A1 gene encodes a member of the fibrillar collagen family and plays a role in the calcification of cartilage and the transition from cartilage to bone.

The encoded protein product is a preprotein. It contains an N-terminal signal peptide followed by an N-terminal propeptide, a mature peptide, and a C-terminal propeptide. The N-terminal propeptide contains N-terminal thrombospondin-like and laminin G-like domains. The mature peptide is a large triple-helical region. The C-terminal propeptide, also known as the COLFI domain, plays a critical role in tissue growth and repair.

Diseases associated with COL27A1 include:

• Steel syndrome (OMIM:615155), a rare genetic bone disorder characterized by short stature, bilateral congenital hip dislocation, radial head dislocation, carpal coalition, scoliosis, pes cavus, and atlantoaxial subluxation. Dysmorphic facial features include a broad forehead, broad nasal bridge, hypertelorism, and mild midface hypoplasia. An association with bilateral sensorineural hearing loss has also been described (Girisha KM et al. 2022).

And

• fibrochondrogenesis 1, a severe, autosomal recessive, short-limbed skeletal dysplasia characterized clinically by a flat midface with a small nose and anteverted nostrils, significant shortening of all limbs but relatively normal hands and feet, and a small bell-shaped thorax with a bulging abdomen. The ribs are typically short and broad with a metaphyseal depression at both ends (Tompson et al. 2010).

1. Girisha KM et al. (2022) Steel syndrome: report of three patients, including monozygotic twins and review of clinical and mutation profiles. Eur J Med Genet 65:104521.
2. Kotabagy S et al (2017) Second family provides further evidence for causation of Steel syndrome by biallelic mutations in COL27A1. Clin Genet 92: 323-326.
   
3. Martinez-Frias ML et al (1996) A new case of fibrochondrogenesis from Spain. J Med Genet. 33: 429-431.
4. Pölsler L et al (2020) A Syrian patient with Steel syndrome due to compound heterozygous COL27A1 mutations with colobomata of the eye. Am J Med Genet A 182:730-734.
5. Steel HH et al (1993) A syndrome of dislocated hips and radial heads, carpal coalition, and short stature in Puerto Rican children. J Bone Joint Surg Am 75: 259-264.
6. Tompson SW et al (2010) Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. Am J Hum Genet 87: 708-712.
7. Whitley CB et al (1984) Fibrochondrogenesis: lethal, autosomal recessive chondrodysplasia with distinctive cartilage histopathology. Am J Med Genet 19: 265-275.