A novel Ser40Trp variant in IFITM5 in a family with osteogenesis imperfecta and review of the literature

Clin Dysmorphol. 2019 Jul;28(3):120-125. doi: 10.1097/MCD.0000000000000279.

Abstract

Osteogenesis imperfecta, is a genetically and clinically heterogeneous connective tissue disorder that disrupts bone architecture, making it fragile and more prone to fractures. While more than 85% of cases are due to variants in COL1A1 and COL1A2, variants in noncollagen genes have been identified in the remaining cases. The recurring heterozygous variant in IFITM5 (c.-14C>T) leads to osteogenesis imperfecta type V, a second missense variant in IFITM5 (c.119C>T, p.Ser40Leu) leads to phenotype resembling osteogenesis imperfecta type VI. In this report, we describe the first patient with Ser40Trp variant in IFITM5, who presented with multiple fractures in the prenatal period. She remained fracture free after birth (except for trauma-related fractures during puberty) with normal bone mineral densitometry. Her mother, who did not have a history of fracture, was noted to have somatogonadal mosaicism for this variant and became pregnant with a second child with multiple prenatal fractures, found to have the same variant. To our knowledge, this is the first case of somatogonadal mosaicism in IFITM5. In addition, we have summarized the literature on patients presenting with variant in codon 40 (serine) of IFTIM5 protein.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Bone and Bones
  • Child
  • Collagen Type I / genetics
  • Family
  • Female
  • Heterozygote
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mutation
  • Osteogenesis Imperfecta / genetics*
  • Osteogenesis Imperfecta / metabolism
  • Pedigree
  • Phenotype

Substances

  • Collagen Type I
  • IFITM5 protein, human
  • Membrane Proteins