一例PYGM基因复合杂合突变导致糖原累积症V型的诊断和基因检测分析

doi:10.16288/j.yczz.22-223

遗传 ›› 2022, Vol. 44 ›› Issue (11): 1063-1071.doi: 10.16288/j.yczz.22-223

一例PYGM基因复合杂合突变导致糖原累积症V型的诊断和基因检测分析

蒋琬姿(), 徐昳文, 王依文, 朱肖诚, 龚颖芸, 周红文, 付真真()

南京医科大学第一附属医院内分泌科，南京 210029

收稿日期:2022-06-30 修回日期:2022-09-07 出版日期:2022-11-20 发布日期:2022-09-16
通讯作者: 付真真 E-mail:1995jwz@sina.com;zhenzhen1127@foxmail.com
作者简介:蒋琬姿，在读博士研究生，专业方向：肥胖、脂代谢和罕见代谢病。E-mail: 1995jwz@sina.com。
基金资助:
国家重点研发计划(2019YFA0802701);国家重点研发计划(2018YFA0506904);国家自然科学基金面上项目(82170882);国家自然科学基金重大研究计划培育项目(91854122)

Diagnosis and genetic analysis of a case with glycogen storage disease type V caused by compound heterozygous mutations in the PYGM gene

Wanzi Jiang(), Yiwen Xu, Yiwen Wang, Xiaocheng Zhu, Yingyun Gong, Hongwen Zhou, Zhenzhen Fu()

Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

Received:2022-06-30 Revised:2022-09-07 Online:2022-11-20 Published:2022-09-16
Contact: Fu Zhenzhen E-mail:1995jwz@sina.com;zhenzhen1127@foxmail.com
Supported by:
the National Key Research and Development Program of China(2019YFA0802701);the National Key Research and Development Program of China(2018YFA0506904);the National Natural Science Foundation of China(82170882);the Major Research Plan of the National Natural Science Foundation of China(91854122)

摘要/Abstract

摘要：

糖原累积症V型是一种由肌糖原磷酸化酶(muscle glycogen phosphorylase，PYGM)缺陷引起的常染色体隐性遗传疾病，其临床特征为运动不耐受、再振作现象和血清肌酸激酶水平增高。本文报道了1例中国糖原累积症V型年轻男性患者，运动后双下肢无力、血肌酸激酶升高、肌肉磁共振可见下肢近端后群肌轻度脂肪浸润，基因检测结果显示先证者具有复合杂合型PYGM致病突变，分别为来自母亲的c.308T>C (p.L103P)变异和来自父亲的c.260_261delCT (p.S87Ffs*23)变异，其中前者为新发突变。本研究丰富了PYGM致病基因突变谱，有助于提高临床医生对糖原累积症V型的认识，并为该疾病的进一步遗传学研究提供参考。

关键词: 糖原累积症V型, McArdle病, PYGM, 罕见病

Abstract:

Glycogen storage disease type V is an autosomal recessive genetic disorder caused by muscle glycogen phosphorylase (PYGM) deficiency, which is characterized by exercise intolerance, second wind phenomena and high level of serum creatine kinase. In this study, we reported a Chinese young man with glycogen storage disease type V, with lower extremity weakness after exercise, increased creatine kinase, and slight fat infiltration in the posterior group of thigh muscle by magnetic resonance imaging (MRI). The proband had complex heterozygous PYGM disease-causing mutations, including c.308T>C (p.L103P) variant transmitted from the mother and c.260_261delCT (p.S87Ffs*23) from the father, of which the former was a novel PYGM mutation. This study enriched the PYGM pathogenic gene mutation spectrum, contributed to improve clinicians' understanding of glycogen storage disease type V and provided a reference for further genetic study of the disease.

Key words: glycogen storage disease type V, McArdle disease, PYGM, rare disease

蒋琬姿, 徐昳文, 王依文, 朱肖诚, 龚颖芸, 周红文, 付真真. 一例PYGM基因复合杂合突变导致糖原累积症V型的诊断和基因检测分析[J]. 遗传, 2022, 44(11): 1063-1071.

Wanzi Jiang, Yiwen Xu, Yiwen Wang, Xiaocheng Zhu, Yingyun Gong, Hongwen Zhou, Zhenzhen Fu. Diagnosis and genetic analysis of a case with glycogen storage disease type V caused by compound heterozygous mutations in the PYGM gene[J]. Hereditas(Beijing), 2022, 44(11): 1063-1071.

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临床分级	描述
0	无症状或几乎无症状(轻度运动不耐受，但在任何日常活动中均无功能限制)
I	偶尔在日常生活中运动不耐受、痉挛、肌痛，急性剧烈运动受限；无肌红蛋白尿，无肌肉萎缩或无力
II	I情况下，加上反复劳累性肌红蛋白尿，中度运动受限，日常生活活动受限
III	II情况下，固定肌无力，伴或不伴萎缩，运动及大部分日常生活活动严重受限

c.308T>C(p.L103P)	致病性预测
SIFT	致病
Polyphen2	可能致病
Mutation Taster	致病

一例PYGM基因复合杂合突变导致糖原累积症V型的诊断和基因检测分析

Diagnosis and genetic analysis of a case with glycogen storage disease type V caused by compound heterozygous mutations in the PYGM gene

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