A novel de novo mutation in COL2A1 gene associated with fetal skeletal dysplasia

Taiwan J Obstet Gynecol. 2021 Mar;60(2):359-362. doi: 10.1016/j.tjog.2021.01.017.

Abstract

Objective: Skeletal dysplasias, caused by genetic mutations, are a heterogenous group of heritable disorders affecting bone development during fetal life. Stickler syndrome, one of the skeletal dysplasias, is an autosomal dominant connective tissue disorder caused by abnormal collagen synthesis owing to a genetic mutation in COL2A1.

Case report: We present the case of a 38-year-old multipara woman whose first trimester screening showed a normal karyotype. However, the bilateral femur and humerus length symmetrically shortened after 20 weeks. Next-generation sequencing for mutations in potential genes leading to skeletal dysplasia detected a novel de novo mutation (c.1438G > A, p.Gly480Arg) in COL2A1, causing Stickler syndrome type 1. This pathogenic mutation might impair or destabilize the collagen structure, leading to collagen type II, IX, and XI dysfunction.

Conclusion: We identified a novel de novo mutation in COL2A1 related to the STL1 syndrome and delineated the extent of the skeletal dysplasia disease spectrum.

Keywords: COL2A1 gene; Short extremities; Skeletal dysplasia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Arthritis / diagnosis*
  • Arthritis / embryology
  • Arthritis / genetics*
  • Collagen Type II / genetics*
  • Connective Tissue Diseases / diagnosis*
  • Connective Tissue Diseases / embryology
  • Connective Tissue Diseases / genetics*
  • Female
  • Hearing Loss, Sensorineural / diagnosis*
  • Hearing Loss, Sensorineural / embryology
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Mutation
  • Pregnancy
  • Retinal Detachment / diagnosis*
  • Retinal Detachment / embryology
  • Retinal Detachment / genetics*
  • Syndrome

Substances

  • COL2A1 protein, human
  • Collagen Type II

Supplementary concepts

  • Stickler syndrome, type 1