Open AccessA novel variant of the IFITM5 gene within the 5′‐UTR causes neonatal transverse clavicular fracture: Expanding the genetic spectrum
Author(s) -
Wu Dong,
Wang Yuxin,
Huang Huijuan
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1287
Subject(s) - sanger sequencing , osteogenesis imperfecta , genetics , gene , exome sequencing , biology , untranslated region , mutant , exon , proband , allele , mutation , messenger rna , anatomy
Background Osteogenesis imperfecta (OI) type V is a rare heritable bone disorder caused by pathogenic variants of IFITM5 . Only two mutated alleles in IFITM5 have been identified worldwide, the role of which in OI pathology is not fully understood. Methods A neonatal case of suspected OI, clinically manifested as a rare clavicle transection fracture with delayed early fracture healing, was studied. Subtle variants of OI‐associated genes were analyzed by whole exome sequencing and confirmed by Sanger sequencing. Results A de novo heterozygous pathogenic variant of IFITM5 within the 5′‐UTR (c.‐9C > A) was discovered in the proband. Bioinformatics analysis using a combination of various algorithms predicted that the variant would generate a new in‐frame start codon 9 bp upstream of the original and express a mutant IFITM5 protein with three additional amino acids (Met‐Glu‐Pro). After transfection into a eukaryocyte in vitro, the mutant IFITM5 construct produced a longer transcription product than that of wild‐type IFITM5. Conclusion This study identified a novel pathogenic variant of IFITM5 , which not only manifested the molecular characteristics of IFITM5 , but also provided new evidence for the study of the molecular mechanisms of IFITM5 association with OI.