头围对识别软骨发育低下中N540K突变的高特异性

摘要(中文译文)

软骨发育不良（HCH）是一种以身材矮小伴四肢不成比例短小为特征的骨骼发育异常。其人体测量学及骨骼特征与软骨发育不全非常相似，但程度较轻。70%的受累个体为FGFR3基因突变的杂合子。本研究分析了伴与不伴N540K突变的受累患者在部分人体测量指标上的差异。疾病诊断依据既往标准化的标准：身材矮小、四肢短小及三项或以上X线特征。采用标准方法从外周血白细胞中提取基因组DNA，并对FGFR3基因第10、13和15外显子进行PCR扩增。共研究26例患者（中位年龄7.31岁，范围0.27~20.0岁）。突变组患者的坐高、身体比例及头围（HC）在统计学上存在差异。采用受试者工作特征（ROC）分析，以评估不同头围截断值对识别伴与不伴突变患者的判别能力。结果发现，头围1.86 SD这一界值检测伴突变的HCH患者的敏感性为73.3%，特异性为100%。所有伴突变患者的头围均大于1.86 SD。这些结果有助于更好地阐明HCH的临床-分子关系。

Abstract

Hypochondroplasia (HCH) is a skeletal dysplasia characterized by short stature with disproportionately short arms and legs. Anthopometrics and skeletal features are very similar to achondroplasia but milder. Seventy per cent of affected individuals are heterozygous for a mutation of the FGFR3 gene. Differences in some anthropometric measurements in affected patients with and without N540K mutation were analysed. Diagnosis of the disease was made on the presence of previously standardized criteria: short stature, short limbs and three or more X-ray features. Genomic DNA was extracted from peripheral blood leukocytes by standard procedures. PCR amplification of exons 10, 13 and 15 of FGFR3 was performed. Twenty-six patients were studied (median age was 7.31, range 0.27-20.0 years). Sitting height, body proportions and head circumference (HC) were statistically different in the mutated group. Receiver Operating Characteristic (ROC) analysis was carried out in order to estimate the discriminating power of different cut-off points of HC for recognizing patients with and without the mutation. A figure of 1.86 SD for HC was found to have a sensitivity of 73.3% and specificity of 100% for detecting HCH patients with the mutation. All of them had a HC greater than 1.86?SD. These results contribute to a better characterization of the clinical-molecular relationships in HCH.

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