Sillén A, Sørensen T, Kantola I, Friis M L, Gustavson K H, Wadelius C
Department of Clinical Genetics, University Hospital, Uppsala, Sweden.
Am J Med Genet. 1997 Mar 3;69(1):102-6. doi: 10.1002/(sici)1096-8628(19970303)69:1<102::aid-ajmg20>3.0.co;2-s.
Familial hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder characterised by episodic attacks of paralysis of varying severity. Recently, linkage was found to markers in 1q31-32 and to the gene encoding the muscle DHP-sensitive calcium channel alpha 1-subunit (CACNL1A3). Subsequently, three mutations in this gene were identified in patients with hypoPP: Arg528His, Arg1239His and Arg1239Gly. In this study, two different mutations were found in the CACNL1A3 gene in 13 Scandinavian families, 10 of whom have the Arg528His mutation while 3 families have the Arg1239His. Furthermore, there is evidence of a founder effect in 8 of the 9 Danish hypoPP families investigated, consisting of haplotypes of microsatellite markers close to and within the CACNL1A3 gene and of the geographic origin of the families. For the first time, reduced penetrance in males with the Arg528His mutation was found in several cases.
家族性低钾性周期性麻痹（低钾型周期性麻痹）是一种常染色体显性疾病，其特征为发作性的、严重程度各异的麻痹。最近，发现该病与1q31 - 32区域的标记以及编码肌肉二氢吡啶敏感性钙通道α1亚基（CACNL1A3）的基因存在连锁关系。随后，在低钾型周期性麻痹患者中鉴定出该基因的三种突变：Arg528His、Arg1239His和Arg1239Gly。在本研究中，在13个斯堪的纳维亚家族的CACNL1A3基因中发现了两种不同的突变，其中10个家族具有Arg528His突变，3个家族具有Arg1239His突变。此外，在9个接受调查的丹麦低钾型周期性麻痹家族中的8个家族中，有证据表明存在奠基者效应，这由靠近CACNL1A3基因及其内部的微卫星标记单倍型以及家族的地理起源组成。首次在几例病例中发现携带Arg528His突变的男性存在外显率降低的情况。
