摘要
目的探讨以继发性男性不育症起病的肯尼迪病(KD)患者的临床特点和遗传学病因。方法选择2023年8月因继发性不育5年就诊于烟台毓璜顶医院确诊的1例AR基因的动态突变男性不育症KD患者(先证者)为研究对象。收集先证者的临床资料、实验室及辅助检查结果。采集先证者及其6名家系成员(先证者女儿、母亲、大姐、二姐及外甥1~2)的外周血各为2 mL并提取DNA,应用全外显子组测序(WES)对先证者进行基因检测,使用生物信息学进行雄激素受体(AR)基因进行致病性分析,最后采用荧光探针PCR-毛细管电泳技术,对AR基因进行第1外显子上胞嘧啶-腺嘌呤-鸟嘌呤(CAG)变异三核苷酸重复序列分析,以检测AR基因的动态突变。本研究通过烟台毓璜顶医院伦理委员会审查(审查批号:2024-697)。结果先证者临床表现为非梗阻性无精子症,雄激素敏感性指数异常增高,阴囊超声检查提示睾丸体积小和精囊腺萎缩,WES和生物信息学分析发现先证者AR基因存在异常扩增,荧光探针PCR和毛细管电泳技术验证先证者及其外甥1的AR基因第1外显子上CAG三核苷酸重复序列的重复次数均为52次,均被诊断为KD,而且家系中先证者母亲、大姐、女儿均为该突变携带者,而先证者二姐及外甥2不携带AR基因变异。结论KD作为一种少见的X-连锁隐性遗传病,患者主要临床表现为肌无力、肌萎缩和肌束震颤,而累及生殖系统引起不育症和非梗阻性无精子症起病患者则较罕见,易被漏诊或误诊,基因检测可明确诊断该病患者,需引起临床医师重视。
Objective:To explore the clinical features and genetic basis of a male patient with Kennedy disease(KD)presenting as secondary infertility.Methods:A male patient who had presented at Yantai Yuhuangding Hospital in August 2023 for secondary infertility for 5 years was selected as the study subject.Clinical data,laboratory findings,and auxiliary examination of the patient were collected.Peripheral blood samples were obtained from the patient and his family members.Following DNA extraction,whole-exome sequencing(WES)was carried out.Pathogenicity of candidate variant was predicted by bioinformatics analysis.Fluorescence probe PCR-capillary electrophoresis was employed to analyze the trinucleotide CAG repeat sequence variation in the AR gene to rule out dynamic mutation.This study was approved by the Ethics Committee of Yantai Yuhuangding Hospital(Ethics No.:2024-697).Results:The patient had presented with non-obstructive azoospermia and elevated androgen sensitivity index.Ultrasound scan indicated small testicular volume and seminal vesicle atrophy.WES and bioinformatics analysis revealed abnormal amplification in the patient′s AR gene.Fluorescence probe PCR and capillary electrophoresis confirmed that both the proband and his nephew had harbored 52 CAG trinucleotide repeats in exon 1 of the AR gene,confirming the diagnosis of KD.The proband′s mother,elder sister,and daughter were identified as carriers of the variant,while his second elder sister did not carry the mutation.Conclusion:As a rare X-linked recessive genetic disease,KD mainly manifests with muscle weakness,myasthenia gravis and myofascial tremor,while cases with infertility and non-obstructive azoospermia as the initial symptoms are rare and can be easily missed.Diagnosis made by genetic testing needs to be taken seriously by the clinicians.
作者
陈杰
靳银山
张学宝
崔元庆
王雄
Chen Jie;Jin Yinshan;Zhang Xuenbao;Cui Yuanqing;Wang Xiong(Reproductive Medicine Center,Yantai Yuhuangding Hospital Affiliated to Qingdao University,Yantai,Shandong 264000,China)
出处
《中华医学遗传学杂志》
2025年第12期1496-1501,共6页
Chinese Journal of Medical Genetics
基金
山东省自然科学基金(ZR2023MH154)。
