title: Identification of a novel heterozygous mutation in exon 50 of the COL1A1 gene causing osteogenesis imperfecta.
abstract: A 19-year-old woman was diagnosed with osteogenesis imperfecta (OI). She had sustained numerous low-trauma fractures throughout her childhood, including a recent pelvic fracture (superior and inferior ramus) following a low-impact fall. She had the classical blue sclerae, and dual energy X-ray absorptiometry (DEXA) bone scanning confirmed low bone mass for her age in the lumbar spine (Z-score was -2.6). However, despite these classical clinical features, the diagnosis of OI had not been entertained throughout the whole of her childhood. Sequencing of her genomic DNA revealed that she was heterozygous for the c.3880_3883dup mutation in exon 50 of the COL1A1 gene. This mutation is predicted to result in a frameshift at p.Thr1295, and truncating stop codon 3 amino acids downstream. To our knowledge, this mutation has not previously been reported in OI.
  
  
  CONCLUSIONS
  OI is a rare but important genetic metabolic bone and connective tissue disorder that manifests a diverse clinical phenotype that includes recurrent low-impact fractures.Most mutations that underlie OI occur within exon 50 of the COL1A1 gene (coding for protein constituents of type 1 pro-collagen).The diagnosis of OI is easily missed in its mild form. Early diagnosis is important, and there is a need for improved awareness of OI among health care professionals.OI is a diagnosis of exclusion, although the key diagnostic criterion is through genetic testing for mutations within the COL1A1 gene.Effective management of OI should be instituted through a multidisciplinary team approach that includes a bone specialist (usually an endocrinologist or rheumatologist), a geneticist, an audiometrist and a genetic counsellor. Physiotherapy and orthopaedic surgery may also be required.
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: S A S
authors.initials: SA
authors.lastname: Aftab
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: N
authors.initials: N
authors.lastname: Reddy
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: N L
authors.initials: NL
authors.lastname: Owen
authors.affiliation: Connective Tissue Disorders Service, Sheffield Diagnostic Genetics Service Sheffield Children's NHS Foundation Trust, Western Bank Sheffield, S10 2TH UK.
authors.forename: R
authors.initials: R
authors.lastname: Pollitt
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: A
authors.initials: A
authors.lastname: Harte
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: P G
authors.initials: PG
authors.lastname: McTernan
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: G
authors.initials: G
authors.lastname: Tripathi
authors.affiliation: Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, University of Warwick Clifford Bridge Road, Coventry, CV2 2DX UK.
authors.forename: T M
authors.initials: TM
authors.lastname: Barber