Massive parallel sequencing and osteogenesis imperfecta: An essential tool for forensic investigation over child abuse

• Published in: Forensic science international. Genetics supplement series Vol. 7; no. 1; pp. 103 - 104
• Main Authors: Onofri, V., Pesaresi, M., Turchi, C., Tagliabracci, A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-12-2019
• Subjects: Child abuse; Genetics; Osteogenesis imperfecta; Osteogenesis imperfecta; Genetics; Child abuse
• ISSN: 1875-1768; 1875-175X
• DOI: 10.1016/j.fsigss.2019.09.040

Osteogenesis imperfecta (OI) is a rare disease of collagen synthesis causing bone fragility. Also called “glass bone disease” since it manifests as spontaneous fractures, it is classified into nine types, both with dominant and recessive transmission. In 95% of cases OI is caused by mutations in COL1A1 and COL1A2 genes encoding the alpha1 and alpha2 chains of type 1 collagen, mainly null variants caused by frame-shift/nonsense mutations or splicing defects. In infants the differential diagnosis include not-accidental trauma, so child abuse. Families suspected of abuse often provide an unverified history of frequent fractures; conversely, the family history of individuals with OI often does not reveal any other affected individuals because of a de novo pathogenic variant in the proband or the presence of a mild phenotype in relatives. Therefore, legal medicine unit with DNA lab is crucial in these cases since it could early collect living or autopsy samples when a child abuse is suspected and then test DNA. We set up a MPS (massively parallel sequencing) panel including the coding regions of COL1A1 and COL1A2 and other 11 genes known to cause OI. We presented a case of suspected abuses in 2-month-old baby. MPS libraries were sequenced by Ion Torrent PGM platform; pathogenic variants and VUS (variants of uncertain significance) were confirmed by Sanger sequencing and familial segregation study was performed to better characterize the clinical significance of the mutation. This study remarks that MPS could help not only for identification, ancestry/phenotyping or molecular autopsy applications but also for forensic investigation over child abuse. The usefulness of this assay for diagnostic projects on victims of abuse together with post-mortem cases is discussed.