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目的:探讨脆性X染色体综合征(FXS)家系患者包括生殖在内的若干临床表现及其遗传学特征。方法:通过问诊、睾丸超声检查、精液分析、生殖激素水平测定、外周血核型检查、Y染色体微缺失检查等手段收集1例FXS家系的临床资料,采用Southern印迹测定该家系多个成员X染色体长臂脆性X智力低下-1(FMR1)基因的CGG三联重复序列的大小,确定其FMR1基因的状态(正常、前突变、全突变)并绘制家系图谱。结果:1经FMR1基因突变检测,该家系4代共34例成员中有3男1女系FMR1全突变患者,占家系成员的11.76%;有9女系FMR1前突变患者,占家系成员的26.47%。2包括先证者在内的2例全突变FXS男性患者睾丸体积>30 ml,精子浓度高(>250×10~6/ml),平均精子活力为50.5%,正常形态精子百分率为17.5%,精子核DNA碎片率指数(DFI)为18.5%;生殖激素仅示睾酮低下;外周血染色体核型未见异常,Y染色体也未见缺失。3Ⅱ代4例前突变女性患者中有1例患有卵巢早衰(POF),3例患有子宫肌瘤。结论:该家系中部分FXS男性患者表现为巨睾症和多精子症,其余精子参数正常;在世代传递中前突变患者可扩展为全突变,且男性的全突变风险高于女性,对于>80的CGG三联重复序列前突变患者,其突变遗传给后代及前突变扩展为全突变的风险会有所增加。建议有生育要求者接受基因检测、临床指导和遗传咨询,必要时行产前诊断与植入前胚胎学诊断。
Objective: To investigate some clinical manifestations and their genetic characteristics including family history in patients with Fragile X chromosome syndrome (FXS). Methods: The clinical data of one case of FXS pedigree were collected by means of interrogation, testicular ultrasound, semen analysis, reproductive hormone test, peripheral blood karyotype examination and Y chromosome microdeletion test. Chromosomal Long Arm Fragile X mental retardation -1 (FMR1) CGG gene triple duplication of the size of the gene to determine its FMR1 status (normal, pre-mutation, full mutation) and draw the family map. A total of 34 males and 4 females with 3 male and 1 female FMR1 mutations were detected in the 4 generations of the pedigree, accounting for 11.76% of the total pedigrees. There were 9 pre-FMR1 mutations in 26 pedigrees, accounting for 26.47% of the total pedigrees. 2 The testis volume> 30 ml, sperm concentration (> 250 × 10 ~ 6 / ml), average sperm motility was 50.5%, normal sperm percentage was 17.5% Sperm DNA fragmentation index (DFI) was 18.5%; reproductive hormones only showed low testosterone; peripheral blood chromosomal karyotype no abnormalities, Y chromosome was also missing. One of the 4 pre-mutation female patients had premature ovarian failure (POF) and 3 had uterine fibroids. CONCLUSIONS: Some FXS male patients in this pedigree are characterized by giant testicles and polyps, and the rest of the sperm parameters are normal. Patients who pass the mid-life transmission can be extended to full mutation, and the risk of total mutation in men is higher than that in women Of patients with CGG triple-mutation repeat mutations have an increased risk of inheritance of mutations to their offspring and their pre-mutation to full mutation. It is recommended that those who have childbearing requirements to accept genetic testing, clinical guidance and genetic counseling, if necessary, prenatal diagnosis and preimplantation embryology diagnosis.