Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta.
Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta.
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DOI：
10.1186/s13023-015-0370-2
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发表时间：
2015-12-01
影响因子：
3.7
通讯作者：
Lin SP
中科院分区：
文献类型：
--
作者：
Lin HY;Chuang CK;Su YN;Chen MR;Chiu HC;Niu DM;Lin SP
成骨不全症（OI）是一种先天性疾病，其特征是骨脆性增加和骨量低。通过直接测序对来自 37 个无关家庭的 72 名 OI 型 I、III 或 IV 患者（27 名男性和 45 名女性；年龄范围 0.2-62 岁）进行了 COL1A1 或 COL1A2 突变的存在调查。还记录了这些患者的临床特征。鉴定出 37 个 COL1A1 和 COL1A2 突变，其中 28 个 COL1A1 突变和 9 个 COL1A2 突变。十五 (41%) 是新突变，十二 (32%) 是家族突变。对他们的病历进行审查后发现，这 72 名患者可分为 I 型（n = 42）、III 型（n = 5）和 IV 型（n = 25）。 29 名患者患有螺旋突变（由三螺旋的 Gly-X-Y 三联体结构域内的甘氨酸取代引起），42 名患者患有单倍体不足突变（由移码、无义和剪接位点突变引起）。与单倍体不足相比，螺旋突变患者的骨骼表型受损更严重，包括身高较短、骨密度较低、步行能力较差、牙本质发育不全和脊柱侧凸的表现更频繁（p<<0.05）。基因型和表型数据库有望促进成骨不全患者更好的遗传咨询和医疗护理。本文的在线版本 (doi:10.1186/s13023-015-0370-2) 包含补充材料，可供授权用户使用。
Osteogenesis imperfecta (OI) is a congenital disorder characterized by increased bone fragility and low bone mass. The presence of COL1A1 or COL1A2 mutation was investigated by direct sequencing in 72 patients with OI type I, III, or IV (27 males and 45 females; age range 0.2-62 years) from 37 unrelated families. The clinical features of these patients were also recorded. Thirty-seven COL1A1 and COL1A2 mutations were identified, including 28 COL1A1 mutations and 9 COL1A2 mutations. Fifteen (41 %) were novel mutations, and twelve (32 %) were familial mutations. A review of their medical records revealed that the 72 patients could be classified into OI type I (n = 42), III (n = 5), and IV (n = 25). Twenty-nine patients had helical mutations (caused by the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix), and 42 had haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations). Compared with haploinsufficiency, the patients with helical mutations had more severely impaired skeletal phenotypes, including shorter height, lower bone mineral density, poorer walking ability, more frequent manifestations of dentinogenesis imperfecta and scoliosis (p < 0.05). Genotype and phenotype databases are expected to promote better genetic counseling and medical care of patients with OI. The online version of this article (doi:10.1186/s13023-015-0370-2) contains supplementary material, which is available to authorized users.