Autosomal recessive Stickler syndrome resulting from a COL9A3 mutation

Am J Med Genet A. 2018 Dec;176(12):2887-2891. doi: 10.1002/ajmg.a.40647. Epub 2018 Nov 18.


Stickler syndrome is a connective tissue disorder characterized by hearing loss, ocular anomalies, palatal defects, and skeletal abnormalities. The autosomal dominant form is the most common, but autosomal recessive forms have also been described. We report the second case of autosomal recessive Stickler syndrome due to homozygosity for a loss of function mutation in COL9A3, which encodes the α3 chain of type IX procollagen. The clinical features were similar to the previously described COL9A3 Stickler syndrome family, including moderate to severe sensorineural hearing loss, high myopia, and both tibial and femoral bowing at birth. Radiographs demonstrated abnormal capital femoral epiphyses and mild irregularities of the vertebral endplates. This case further establishes the phenotype associated with mutations in this gene. We suggest that loss of the α3 chain of type IX collagen results in a Stickler syndrome phenotype similar to that of the other autosomal recessive forms caused by mutations in genes encoding the α1 and α2 chains of type IX collagen.

Keywords: COL9A3; Stickler syndrome; autosomal recessive; type IX procollagen.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthritis / diagnosis*
  • Arthritis / genetics*
  • Child
  • Collagen Type IX / genetics*
  • Connective Tissue Diseases / diagnosis*
  • Connective Tissue Diseases / genetics*
  • DNA Mutational Analysis
  • Exome Sequencing
  • Genes, Recessive*
  • Hearing Loss, Sensorineural / diagnosis*
  • Hearing Loss, Sensorineural / genetics*
  • Homozygote
  • Humans
  • Infant, Newborn
  • Mutation*
  • Phenotype
  • Radiography
  • Retinal Detachment / diagnosis*
  • Retinal Detachment / genetics*


  • COL9A3 protein, human
  • Collagen Type IX

Supplementary concepts

  • Stickler syndrome, type 1