进行性骨干发育不良一家系临床特征和转化生长因子β1基因突变

Clinical features and transforming growth factor β1 gene mutation in a family with progressive diaphyseal dysplasia

目的通过临床诊断的1个进行性骨干发育不良(progressive diaphyseal dysplasia,PDD)家系,分析家系中患病父子的临床特征及影像学表现,并检测致病基因--转化生长因子β1 (transforming growth factor beta 1,TGFβ1)突变位点。方法收集先证者及其子临床资料,完善辅助检查,并采用Sanger测序法检测家系成员TGFβ1基因突变位点。结果临床血液检测发现先证者父子血碱性磷酸酶和骨代谢指标显著升高;摄片可见先证者头颅、骨盆密度增加,双侧尺桡骨和胫腓骨骨干增粗、骨皮质增厚、密度不均以及髓腔狭窄。全身骨显像示先证者父子颅骨及四肢骨放射性摄取增高,骨代谢异常活跃。致病基因突变检测发现先证者及其子均存在TGFβ1基因4号外显子c.652C>T (p.R218C)杂合错义突变,家系其他成员未检测出该位点突变。结论 PDD临床特征主要为幼儿起病、步态异常、体型瘦小、肌肉萎缩。影像学检查可见四肢骨骨干呈对称性增粗、皮质增厚以及受累部位髓腔狭窄等典型表现。该病的致病基因为TGFβ1基因突变。

Objective To investigate the clinical features,imaging manifestations of the proband and son,and pathogenic mutation of transforming growth factor beta 1(TGFβ1) gene in a progressive diaphyseal dysplasia(PDD) family.Methods A proband and his son with abnormal gait were included.Clinical data of two patients were collected and we completed accessory examinations.TGFβ1 gene mutation of two patients was detected by Sanger sequencing.Results Biochemical tests of the two patients showed high levels of bone turnover markers.Imaging examination of the proband indicated increased density of skull and pelvis,the thickening in diaphysis of limb bones and the cortical bone.Whole body skeletal imaging found increased abnormal radionuclide uptake in bones of skull and limbs in the two patients.Gene detection found that both the proband and his son had heterozygous mutation of TGFβ1(c.652 C>T),but this mutation was not found in other members of this family.Conclusions Onset in infants,abnormal gait,slender body and muscular atrophy are known to be characteristic of PDD.Imaging will be featured with thickening and sclerosis in the diaphysis of the limbs and cortical bone.Whole body skeletal imaging shows a typical change in abnormal bone metabolism and the molecular mechanism is mainly caused by TGFβ1 gene mutation in PDD.