中国南方汉族散发早发性帕金森综合征的parkin基因突变分析

Analysis of parkin gene mutations in Han Chinese with sporadic early-onset parkinsonism in southern China

目的 探讨中国南方汉族散发早发性帕金森综合征（early onset parkinsonism,EOP）的parkin基因突变特点.方法 应用实时荧光定量PCR技术结合DNA直接测序技术对156例中国南方汉族散发EOP患者进行parkin基因突变分析.结果 19例患者parkin基因突变,包括15例杂合突变、2例纯合突变、2例复杂杂合突变.17例患者外显子重排突变,其中12例外显子缺失突变,5例外显子双重重复突变.此外,3例患者存在点突变和（或）小片段缺失突变,其中ⅣS9＋18C＞T、c.202-203delAG为已报道突变,c.813delT为未报道的新突变;parkin基因突变位点主要分布在其1～7号外显子.无parkin基因突变与有parkin基因突变的患者在临床表现及病情严重程度方面差异无统计学意义,但发病年龄[（40.9±6.8）岁与（35.5±10.0）岁,Z=-2.271,P=0.023）]、病程[（4.4±3.6）年与（7.6±4.0）年,Z=-3.680,P=0.000）]等方面差异有统计学意义.结论 中国南方汉族散发EOP患者parkin基因突变的频率为12.18%（19/156）,外显子重排突变是其重要突变类型;外显子缺失突变是主要的突变形式;parkin基因1～7号外显子为突变热点.parkin基因突变与无parkin基因突变的EOP患者在临床表型上无明显差异,但其发病年龄较轻,病程较长,进展较缓慢.

Objective To investigate the spectrum and features of parkin gene mutations in Chinese patients with sporadic early-onset Parkinsonism （EOP） in southern China.Methods All 156 Han Chinese patients with sporadic EOP were screened for mutations in parkin gene using SYBR Green Ⅰ Real-time PGR combined with sequencing of the entire coding region of the gene.Results Nineteen cases carried parkin mutations, including 2 homozygous, 2 compound heterozygous and 15 heterozygous mutations.Seventeen parkin gene rearrangement mutations （ 12 exon deletions and 5 exon duplications） and three small sequence mutations （ⅣS9 ＋ 18C 〉 T,c.202-203delAG and c.813delT） were identified.The c.813delT is a novel mutation.The segment between exon 1 and 7 are mutational hot spot.Cases with parkin mutations showed no difference in initial symptoms, cardinal symptoms and disease severity, compared with cases without parkin mutations.But patients with parkin mutations showed significant earlier onset age （ （ 40.9 ± 6.8 ） years vs （35.5 ± 10.0） years, Z = -2.271, P 〈0.05） and longer disease duration （ （4.4 ±3.6） years vs （7.6 ±4.0） years,Z = - 3.680, P 〈 0.05 ） than those without parkin mutation.Conclusions The frequency of parkin gene mutation was 12.18% in Han Chinese patients with sporadic EOP.Rearrangement mutation may be the predominant type of mutations.The exon deletion is a main mutation style.The sequence fragment between exon 1 and 7 of the parkin gene are mutational hot spots.There were no significant differences in clinical features between cases with parkin mutation and those without.However, our patient with parkin mutations showed a significantly earlier onset age, longer disease duration and slower progression than those without parkin mutation.