Deprez Liesbet, Claes Lieve R F, Claeys Kristl G, Audenaert Dominique, Van Dyck Tine, Goossens Dirk, Van Paesschen Wim, Del-Favero Jurgen, Van Broeckhoven Christine, De Jonghe Peter
Neurogenetics Group, Department of Molecular Genetics VIB8, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Hum Genet. 2006 Jan;118(5):618-25. doi: 10.1007/s00439-005-0077-x. Epub 2005 Nov 5.
Febrile seizures (FS) represent the most common seizure disorder in childhood and contribution of a genetic predisposition has been clearly proven. In some families FS is associated with a wide variety of afebrile seizures. Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS, atypical febrile seizures (FS+) and afebrile generalized and partial seizures. Mutations in the genes SCN1B, SCN1A and GABRG2 were identified in GEFS+ families. GEFS+ is genetically heterogeneous and mutations in these three genes were detected in only a minority of the families. We performed a 10 cM density genome-wide scan in a multigenerational family with febrile seizures and epilepsy and obtained a maximal multipoint LOD score of 3.12 with markers on chromosome 5q14.3-q23.1. Fine mapping and segregation analysis defined a genetic interval of approximately 33 cM between D5S2103 and D5S1975. This candidate region overlapped with a previously reported locus for febrile seizures (FEB4) in the Japanese population, in which MASS1 was proposed as disease gene. Mutation analysis of the exons and exon-intron boundaries of MASS1 in our family did not reveal a disease causing mutation. Our linkage data confirm for the first time that a locus on chromosome 5q14-q23 plays a role in idiopathic epilepsies. However, our mutation data is negative and do not support a role for MASS1 suggesting that another gene within or near the FEB4 locus might exist.
热性惊厥（FS）是儿童期最常见的惊厥性疾病，遗传易感性的作用已得到明确证实。在一些家庭中，FS与多种无热惊厥相关。热性惊厥附加症伴全面性癫痫（GEFS+）是一种家族性癫痫综合征，具有一系列表型，包括FS、非典型热性惊厥（FS+）以及无热全面性和局灶性惊厥。在GEFS+家族中已鉴定出SCN1B、SCN1A和GABRG2基因的突变。GEFS+具有遗传异质性，这三个基因的突变仅在少数家族中被检测到。我们对一个患有热性惊厥和癫痫的多代家族进行了10 cM密度的全基因组扫描，在5号染色体5q14.3 - q23.1上的标记获得了最大多点LOD分数为3.12。精细定位和分离分析确定了D5S2103和D5S1975之间约33 cM的遗传区间。该候选区域与日本人群中先前报道的一个热性惊厥位点（FEB4）重叠，其中MASS1被提议作为致病基因。对我们家族中MASS1外显子和外显子 - 内含子边界的突变分析未发现致病突变。我们的连锁数据首次证实5号染色体5q14 - q23上的一个位点在特发性癫痫中起作用。然而，我们的突变数据为阴性，不支持MASS1的作用，提示FEB4位点内或附近可能存在另一个基因。
