眼咽型肌营养不良症一家系临床及分子生物学特征分析

doi:10.3969/j.issn.1672-6731.2021.06.006

中国现代神经疾病杂志 ›› 2021, Vol. 21 ›› Issue (6): 460-465. doi: 10.3969/j.issn.1672-6731.2021.06.006

2 眼咽型肌营养不良症一家系临床及分子生物学特征分析

黄铠¹, 李文武², 刘红仙¹, 孙浩¹, 李志宏², 褚嘉祐¹, 杨昭庆¹

1 650118 昆明, 中国医学科学院北京协和医学院医学生物学研究所;
2 675000 云南省楚雄彝族自治州人民医院神经内科

收稿日期:2021-06-15 出版日期:2021-06-25 发布日期:2021-06-26
通讯作者: 杨昭庆,Email:zyang@imbcams.com.cn
基金资助:
云南省地方本科高校（部分）基础研究面上项目（项目编号：2018FH001-082）；云南省高层次卫生健康技术人才培养专项（项目编号：L-2018003）

Clinical symptoms and molecular biology research in a family with oculopharyngeal muscular dystrophy

HUANG Kai¹, LI Wen-wu², LIU Hong-xian¹, SUN Hao¹, LI Zhi-hong², CHU Jia-you¹, YANG Zhao-qing¹

1 Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, Yunnan, China;
2 Department of Neurology, The People's Hospital of Chuxiong Yi Autonomous Prefecture, Chuxiong 675000, Yunnan, China

Received:2021-06-15 Online:2021-06-25 Published:2021-06-26
Supported by:
This study was supported by the Basic Research Project of Local Undergraduate Universities (Part) in Yunnan (No. 2018FH001-082), and the Special Project for Training High-level Health Technical Personnel in Yunnan (No. L-2018003).

摘要/Abstract

摘要：

目的总结一眼咽型肌营养不良症（OPMD）家系的临床及分子生物学特征。方法收集云南省楚雄彝族自治州的一OPMD家系的临床资料，并对其中6位家族成员行外周静脉血基因组DNA分离，通过聚合酶链反应（PCR）、TA克隆和Sanger测序，检测PABPN1基因变异特点。结果该OPMD家系中4位成员均于50岁后发病，以眼睑下垂为首发症状，进行性加重并出现以吞咽困难为表现的咽部肌群受累。基因检测显示，先证者（Ⅱ3）及其二姐（Ⅱ2）、四弟（Ⅱ4）和五妹（Ⅱ5）均存在PABPN1基因外显子1（GCN）异常重复扩增，即（GCN）₁₀/（GCN）₁₃，在家系中呈现显性遗传模式，最终诊断为OPMD，该家系明确为OPMD家系。结论杂合子（GCN）₁₃异常重复扩增是该OPMD家系成员患病之病因，临床症状在发现疾病中起主导作用，基因检测是明确诊断的"金标准"，可为治疗方案的选择以及遗传咨询提供主要依据。

关键词: 肌营养不良, 眼咽, 聚核苷酸嘌呤转移酶, 基因, 突变, 系谱

Abstract:

Objective To investigate the clinical symptoms and molecular biological characteristics in a family with oculopharyngeal muscular dystrophy (OPMD). Methods Clinical data of the family members were collected. Genomic DNA were isolated from peripheral blood of 6 family members including the probands for polymerase chain reaction (PCR). TA cloning followed by Sanger DNA sequencing was conducted for detecting PABPN1 gene mutations. Results The first symptom of the 4 family members in OPMD pedigree was ptosis at 50-years-old. The clinical symptoms of pharyngeal muscles involved in gradually dysphagia. Genetic testing found:the proband (Ⅱ 3), the second sister of the proband (Ⅱ 2), the fourth brother of the proband (Ⅱ 4), and the fifth sister of the proband (Ⅱ 5) had abnormal amplification of (GCN) repeat, (GCN)₁₀/(GCN)₁₃ in exon 1 of PABPN1 gene, which was identified in 4 members of the family who conducted the genetic testing. There was a dominant inheritance pattern in the lineage. The final diagnosis was OPMD, and the family was diagnosed as OPMD. Conclusions Clinical symptoms play a decisive role in the detection of the disease, thus genetic testing is the ctritical factor to the diagnosis and prevention of oculopharyngeal muscular dystrophy, which provides necessary information for choosing treatments and genetic counseling.

Key words: Muscular dystrophy, oculopharyngeal, Polynucleotide adenylyltransferase, Genes, Mutation, Pedigree

黄铠, 李文武, 刘红仙, 孙浩, 李志宏, 褚嘉祐, 杨昭庆. 眼咽型肌营养不良症一家系临床及分子生物学特征分析[J]. 中国现代神经疾病杂志, 2021, 21(6): 460-465.

HUANG Kai, LI Wen-wu, LIU Hong-xian, SUN Hao, LI Zhi-hong, CHU Jia-you, YANG Zhao-qing. Clinical symptoms and molecular biology research in a family with oculopharyngeal muscular dystrophy[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(6): 460-465.

http://journal11.magtechjournal.com/cjcnn/CN/Y2021/V21/I6/460

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