Genotype and Phenotype Analysis of Patients With Sporadic Periodic Paralysis
Genotype and Phenotype Analysis of Patients With Sporadic Periodic Paralysis
复制标题
DOI：
10.1097/maj.0b013e31822b430c
复制
发表时间：
2012-04-01
影响因子：
3.1
通讯作者：
Lin, Shih-Hua
中科院分区：
文献类型：
--
作者：
Sung, Chih-Chien;Cheng, Chih-Jen;Lin, Shih-Hua
简介：散发性周期性麻痹（SPP）是亚洲低钾型周期性麻痹（HPP）的第二大病因，其表现与家族性周期性麻痹（FPP）相似，由骨骼肌钙（Ca2+）（CACNA1S）和钠（Na+）（SCN 4A）通道的基因突变引起。作者确定SPP是否与FPP具有相似的基因型和表型。研究方法：60例SPP患者没有瘫痪家族史、甲状腺功能检查异常和其他可识别的HPP原因，8例FPP患者入选。从所有SPP和FPP患者的血液白细胞中分离基因组DNA。对CACNA1S和SCN4A的整个S4片段进行了遗传分析。表型分析包括临床表现、实验室数据和诱发事件。结果如下：所有FPP患者都有CACNA1S或SCN4A突变，但只有4例SPP患者有CACNA1S（R1239 H）和SCN4A（R669 x2，R1135 H）的新发突变。除了发病年龄晚之外，具有新发突变的SPP患者表现出与FPP患者难以区分的表型。没有突变的SPP患者也有较晚的发病年龄，明显少于FPP患者的瘫痪发作，以及无法识别的促发因素。结论：少数SPP患者存在CACNA1S或SCN4A的新发突变，可能存在FPP的变异。大多数SPP患者，即CACNA1S和SCN4A没有突变的患者，代表了HPP患者的一个独特亚组，这种形式的SPP通常在较晚的年龄出现，与较少的发作相关，并且缺乏明显的触发因素。
Introduction: Sporadic periodic paralysis (SPP), the second leading cause of hypokalemic periodic paralysis (HPP) in Asia, has a presentation similar to that of familial periodic paralysis (FPP) and is caused by gene mutations in the calcium (Ca2+) (CACNA1S) and sodium (Na+) (SCN4A) channels of skeletal muscle. The authors determined whether SPP shares similar genotype and phenotype with FPP. Methods: Sixty SPP patients who did not have a family history of paralysis, abnormal thyroid function tests and other identifiable causes of HPP, and 8 FPP patients were enrolled. Genomic DNA was isolated from blood leukocytes of all SPP and FPP patients. Genetic analysis of whole S4 segment in CACNA1S and SCN4A was performed. Phenotypic analysis included clinical presentations, laboratory data and precipitating events. Results: All FPP patients had mutations in either CACNA1S or SCN4A, but only 4 SPP patients had de novo mutations in CACNA1S (R1239H) and SCN4A (R669x2, R1135H). SPP patients with de novo mutations manifested a phenotype indistinguishable from that of FPP patients except a later age of onset. SPP patients without mutations also had a later age of onset, significantly fewer attacks of paralysis than FPP patients, and unidentifiable precipitating factors. Conclusion: A minority of SPP patients had de novo CACNA1S or SCN4A mutations and may have a variant of FPP. The majority of SPP patients, those without mutations in CACNA1S and SCN4A, represent a unique subgroup of HPP patients, and this form of SPP usually manifests at a later age, is associated with fewer attacks and lacks apparent triggering factors.