Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.-14C>T mutation in all patients
Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.-14C>T mutation in all patients
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DOI：
10.1136/jmedgenet-2012-101307
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Glorieux, Francis H.
中科院分区：
文献类型：
--
作者：
Rauch, Frank;Moffatt, Pierre;Glorieux, Francis H.
研究背景成骨不全（OI）V型是一种常染色体显性遗传的骨脆性疾病，我们在十年前就已经描述过了。最近的研究表明，OI V型是由复发性c. IFITM 5中的14 C>T突变。在本研究中，我们评估了所有在我们机构诊断为OI V型的患者是否存在IFITM 5突变。方法通过桑格测序分析了42例OI V型患者（年龄：2-67岁; 18例女性）基因组DNA中IFITM 5外显子1的存在。所有个体均检测到IFITM 5基因14 C>T突变。疾病严重程度的指标差异很大：身高z评分（n=38）范围为-8.7至-0.1，中位数为-3.5。男性（N=15）和女性（N=10）的中位最终身高分别为147 cm和145 cm。未接受双膦酸盐治疗的腰椎区域骨密度z评分（n=29）在-7.7和-0.7之间，中位数为-5.3。脊柱侧凸是目前在57%，椎体压缩性骨折在90%的patients.Conclusions即使致病突变是相同的患者与OI V型，个体间的表型变异是相当大的。
Background Osteogenesis imperfecta (OI) type V is an autosomal dominant bone fragility disorder that we had described a decade ago. Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5. In the present study, we assessed all patients diagnosed with OI type V at our institutions for the presence of the IFITM5 mutation.Methods IFITM5 exon 1 was analysed by Sanger sequencing in genomic DNA from 42 patients with OI type V (age: 2-67 years; 18 female).Results The c.-14C>T mutation of IFITM5 was detected in all individuals. Indicators of disease severity varied widely: Height z-scores (n=38) ranged from -8.7 to -0.1, median -3.5. Median final height was 147 cm in men (N=15) and 145 cm in women (N=10). Lumbar spine areal bone mineral density z-scores in the absence of bisphosphonate treatment (n=29) were between -7.7 and -0.7, median -5.3. Scoliosis was present in 57%, vertebral compression fractures in 90% of patients.Conclusions Even though the disease-causing mutation is identical among patients with OI type V, the interindividual phenotypic variability is considerable.