儿童Hutchinson-Gilford早老症六例分析

Analysis on six cases of Hutchinson-Gilford progeria syndrome

目的对6例中国儿童早老症的临床特征进行总结,并对部分患儿的致病基因携带情况进行分析。方法选取6例儿童早老症患儿为研究对象,对其临床资料进行总结,并对其中4例患儿家系进行致病基因测序分析。分别留取研究对象的EDTA抗凝血3 ml,用DNA提取试剂盒提取基因组DNA,然后运用一代测序技术对患儿家系进行核纤层蛋白A/C(LMNA)基因测序,并将测序结果与正常结果比对,寻找致病性突变位点。结果6例早老症患儿均具有典型的临床表现,如严重生长迟缓、特殊皮肤表现、典型颅面表现等,符合文献报道的儿童早老症临床特征。基因测序结果显示,2例患儿携带LMNA c.1824 C>T(p.G608G)经典杂合突变,另外2例分别携带LMNA IVS8-4 C>A、c.1968+2T>C非经典型突变,其中IVS8-4 C>A突变尚未见文献报道。结论在中国儿童中,LMNA经典杂合突变和非经典突变均可导致早老症的发生。儿童早老症患儿具有典型的临床表现,临床容易诊断。致病基因测序发现LMNA突变,可进一步明确诊断。

Objective To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome,and to analyze the pathogenic genes carried by some patients.Methods The clinical data of 6 patients were summarized.The pathogenic genes of 4 families were analyzed.Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation.The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA)gene and to identify the pathogenic mutation sites by comparing with normal sequencing results.Results All the children had typical clinical manifestations of the disease which has been previously reported in the literature,such as severe growth retardation,special skin manifestations,and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c.1824C>T(p.G608G).The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c.1968+2T>C,among which the mutation of IVS8-4 C>A has not been reported.Conclusions In Chinese children,both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging.It is easy to make a diagnosis based on clinical manifestations.Finding of the pathogenic gene may further confirm the diagnosis.