延胡索酸水化酶缺陷相关子宫肌瘤临床特点分析

Clinical characteristics of uterine fibroids associated with fumarate hydratase deficiency.

目的探讨延胡索酸水化酶(FH)基因是否突变的子宫肌瘤的差异,为FH基因突变相关子宫肌瘤的早期诊疗和咨询提供依据。方法选取2018年12月至2019年6月因子宫肌瘤在中国医学科学院北京协和医院行手术治疗的患者91例。术前抽取外周血、术中留取最大子宫肌瘤组织行全外显子测序,比较无FH基因胚系突变组(81例)和突变组(10例)的临床资料、病理类型、基因突变类型的差异。结果(1)无FH基因突变组和突变组患者的平均年龄分别为(36.0±6.5)岁和(23.6±4.7)岁,差异有统计学意义(P<0.05)。两组单发肌瘤比例分别为33.3%(27/81)和10.0%(1/10),差异有统计学意义(P<0.05)。两组既往存在子宫肌瘤剔除术史的患者分别占3.7%(3/81)和80.0%(8/10),差异有统计学意义(P<0.05)。(2)无FH基因突变组病理类型为平滑肌瘤患者占92.6%(75/81),富于细胞性平滑肌瘤患者占7.4%(3/81),突变组则分别为30.0%(3/10)和50.0%(5/10),两种病理类型差异均有统计学意义(均P<0.05)。(3)FH基因突变组患者年龄最小为19岁,最大为32岁;子宫肌瘤个数波动在1~150个,其中2例患者子宫肌瘤数量>100个。仅1例患者存在肾癌家族史。9例患者在术后1年之内超声提示复发。(4)FH基因突变组10例患者中2例病理类型为恶性潜能未定的平滑肌瘤,5例为富于细胞性平滑肌瘤,3例为子宫平滑肌瘤。恶性潜能未定的平滑肌瘤的突变位点分别为FH:exon5:c.C703T:p.H235Y;FH:exon5:c.G557A:p.S186N。结论对发病年龄小且多发或单发较大、复发时间短的子宫肌瘤患者,应尽早行FH基因检测来明确诊断,从而获得更有针对性的临床治疗和预防。

Objective To study the difference in uterine fibroids between those with fumarate hydratase(FH)mutaion and those without,and to provide evidence for early diagnosis and treatment and consultation of FH mutation-related uterine fibroids.Methods A total of 91 patients with uterine fibroids receiving surgical treatment in Peking Union Medical College Hospital from December 2018 to June 2019 were recruited.Preoperative peripheral blood and intraoperative maximum uterine fibroid tissue were collected for the whole exon sequencing.The clinical data,pathological types,and gene mutation types of the common group(81,without FH gene mutation)and the FH mutation group(10)were compared.Results The mean age of patients in the common group and FH mutation group were(36.0±6.5)years and(23.6±4.7)years.The proportion of single fibroid in two groups were 33.3%(27/81)and 10.0%(1/10),respectively.Furthermore,patients with previous myomectomy made up 3.7%(3/81)and 80.0%(8/10)of the two groups.These three characteristics between the two groups were all significantly different(P<0.05,P<0.05,P<0.05).In terms of pathological diagnosis,patients with leiomyoma and cellular leiomyoma accounted for 92.6%(75/81)and 7.4%(3/81)in the common group,while the accounted for 30.0%(3/10)and 50.0%(5/10)respectively in FH mutation group.The differences were statistically significant(P<0.05,P<0.05).Patients in the FH mutation group ranged from 19 to 32 years old.The number of uterine fibroids fluctuated between 1-150,and two patients had more than 100 fibroids.Only one patient had a family history of renal cancer.Nine patients had a recurrence within one year of the surgery.Among the 10 patients in the FH mutation group,the pathological type of 2 patients was smooth muscle tumors of uncertain malignant potential,5 patients were cellular leiomyoma,and 3 patients were leiomyoma.The mutation sites of smooth muscle tumors of uncertain malignant potential were FH:exon5:C.703T:p.H235Y,and FH:exon5:C.G557A:p.S186N.Conclusions For patients with early onset age and short-term recurrence of multiple or single giant uterine fibroids,FH gene should be tested to make a clear diagnosis so that targeted clinical treatment and prevention can be given accordingly.