Aftab S A S, Reddy N, Owen N L, Pollitt R, Harte A, McTernan P G, Tripathi G, Barber T M
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.
Connective Tissue Disorders Service, Sheffield Diagnostic Genetics Service Sheffield Children's NHS Foundation Trust, Western Bank Sheffield, S10 2TH UK.
Endocrinol Diabetes Metab Case Rep. 2013;2013:130002. doi: 10.1530/EDM-13-0002. Epub 2013 Jul 1.
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.
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.
一名19岁女性被诊断为成骨不全症（OI）。她在童年时期遭受了多次低创伤性骨折，包括近期一次低冲击力跌倒后发生的骨盆骨折（耻骨上下支）。她有典型的蓝色巩膜，双能X线吸收法（DEXA）骨扫描证实其腰椎骨量低于同龄人（Z值为-2.6）。然而，尽管有这些典型的临床特征，但在她整个童年时期都未考虑过OI的诊断。对其基因组DNA进行测序发现，她在COL1A1基因第50外显子的c.3880_3883dup突变处为杂合子。该突变预计会导致第1295位苏氨酸处的移码，并在下游3个氨基酸处产生截短的终止密码子。据我们所知，该突变此前在OI中尚未有报道。
OI是一种罕见但重要的遗传性代谢性骨和结缔组织疾病，表现出多种临床表型，包括反复发生的低冲击力骨折。OI的大多数潜在突变发生在COL1A1基因的第50外显子内（该基因编码I型前胶原的蛋白质成分）。OI的轻度形式很容易被漏诊。早期诊断很重要，医疗保健专业人员需要提高对OI的认识。OI是一种排除性诊断，尽管关键诊断标准是通过对COL1A1基因内的突变进行基因检测。应通过多学科团队方法对OI进行有效管理，该团队包括骨专科医生（通常是内分泌学家或风湿病学家）、遗传学家、听力测定专家和遗传咨询师。可能还需要物理治疗和骨科手术。
