Case report of the first molecular diagnosis of Stickler syndrome with a pathogenic COL2A1 variant in a Mongolia family

Mol Genet Genomic Med. 2021 Oct;9(10):e1781. doi: 10.1002/mgg3.1781. Epub 2021 Aug 18.

Abstract

Background: Stickler syndrome is a group of connective tissue disorders that can affect eye (myopia, cataract, and retinal detachment), skeleton (spondyloepiphyseal dysplasia and precocious arthritis), craniofacies (midfacial under development and cleft palate), and inner ear (conductive and sensorineural); with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, and COL9A3 procollagen genes cause Stickler syndrome.

Case presentation: A 16-year-old Mongolian girl approached our clinics with retinal detachment. The proband had vitreous degeneration in both eyes, rhegmatogenous retinal detachment in her right eye, a large area of retina degeneration in her left eye, and coupled with severe myopia. No obvious hearing disorder was found, no abnormalities in bones and joints, and her communication and learning capability were also normal. Further clinical examination showed that the patient's other five family members across three generations had vitreous and retina degenerations. Exome sequencing showed a heterozygous splicing variant in COL2A1 in all patients.

Conclusions: In this case report, a pathogenic splicing variant in the COL2A1 gene was identified in a Mongolian family affected with Stickler syndrome type I by exome sequencing. This heterozygous splicing variant in COL2A1 (NM_001844.4:C.2518-1G>A) that may impair splicing, which was suggested by in silico prediction. Next-generation sequencing is helpful for the differential diagnosis of this clinically variable and genetically heterogeneous disorder.

Keywords: COL2A1; stickler syndrome; type I collagenopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arthritis / diagnosis*
  • Arthritis / genetics*
  • Collagen Type II / genetics*
  • Connective Tissue Diseases / diagnosis*
  • Connective Tissue Diseases / genetics*
  • DNA Mutational Analysis
  • Exome Sequencing
  • Family
  • Female
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease
  • Hearing Loss, Sensorineural / diagnosis*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Mongolia
  • Mutation*
  • Pedigree
  • Phenotype
  • Retinal Detachment / diagnosis*
  • Retinal Detachment / genetics*

Substances

  • COL2A1 protein, human
  • Collagen Type II

Supplementary concepts

  • Stickler syndrome, type 1