Polizzi Agata, Incorpora Gemma, Pavone Piero, Ruggieri Martino, Annesi Grazia, Gambardella Antonio, Pavone Lorenzo, Quattrone Aldo
National Centre for Rare Diseases, Superior Institute of Health, Rome, Italy.
Childs Nerv Syst. 2012 Jan;28(1):141-5. doi: 10.1007/s00381-011-1592-9. Epub 2011 Oct 20.
Mutation analysis of the SCN1B, SCN1A and GABRG2 genes in children affected by Genetic (Generalised) Epilepsy with Febrile Seizures plus (GEFS(+)) and their affected and some unaffected family members, coming from a restricted geographic area, was performed.
Eight GEFS(+) families (58 members) diagnosed according to current GEFS(+) criteria were studied.
A heterozygous point mutation A2336G was detected in exon 13 of the SCNA1 gene in three affected members of one family but not in their unaffected relatives; a novel Ile1944Thr mutation was located within the intracellular C-terminal region of the SCNA1 gene in the proband and his healthy father in a second family. In the former family, the proband had dysmorphic features including large forehead, large nasal bridge, pointed nasal tip, triangular nostrils, deep nasolabial folds, thin upper lips with large mouth, congenital gingival hyperplasia with wide gingiva and mental retardation, abnormalities not previously listed in the clinical spectrum of GEFS(+).
Our study confirms that just a few GEFS(+) families have mutations in the five genes classically known and reinforces the genetic and also the phenotypic variability of GEFS(+) featuring clinical manifestations. Question rises whether the cognitive problems seen in two siblings and dysmorphic features in one of them may be related to the channelopathy as it occurs in other well-known ion channel disorders.
对来自一个有限地理区域的患有伴有热性惊厥附加症的遗传性（全身性）癫痫（GEFS(+)）的儿童及其患病和一些未患病的家庭成员进行SCN1B、SCN1A和GABRG2基因的突变分析。
研究了根据当前GEFS(+)标准诊断的8个GEFS(+)家庭（58名成员）。
在一个家庭的3名患病成员中检测到SCN1A基因第13外显子的杂合点突变A2336G，但其未患病亲属中未检测到；在第二个家庭的先证者及其健康父亲中，在SCN1A基因的细胞内C末端区域发现了一个新的Ile1944Thr突变。在前一个家庭中，先证者有畸形特征，包括前额大、鼻梁宽、鼻尖尖、鼻孔呈三角形、鼻唇沟深、上唇薄且嘴巴大、先天性牙龈增生伴牙龈宽和智力发育迟缓，这些异常以前未列入GEFS(+)的临床谱中。
我们的研究证实，只有少数GEFS(+)家庭在经典已知的五个基因中存在突变，并强化了GEFS(+)在临床表现方面的遗传和表型变异性。问题在于，两个兄弟姐妹中出现的认知问题以及其中一人的畸形特征是否可能与通道病有关，就像在其他知名的离子通道疾病中那样。
