Clinical and genetic study on a new Chinese family with benign familial infantile seizures

Abstract

Three loci for benign familial infantile seizures (BFIS, traditionally named benign familial infantile convulsions) have been mapped to the chromosome regions of 19q12-13.1, 2q24, and 16p12-q12. We characterized the clinical features of a newly discovered Chinese family with BFIS and investigated whether it is linked to these loci. A four-generation Chinese family was investigated and nineteen family members were examined. Fourteen microsatellite markers covering the three BFIS loci on the chromosome regions of 19q12-13.1, 2q24, and 16p12-q12 were genotyped. Linkage analysis was performed. The main clinical features of our patients include onset of afebrile seizures between 3 and 10 months, normal psychomotor development, normal interictal electroencephalogram (EEG), and autosomal dominant inheritance. Magnetic resonance imaging (MRI) changes were found in the proband. Two-point LOD scores are < -2.0 at the recombination rate of 0.0 for all the markers on the 2q24 region. Multipoint LOD scores are < -3.0 for the regions of 19q12-13.1 and 16p12-q12. Linkage analysis showed no evidence that the disease gene of this BFIS family is linked to the chromosome regions previously identified as the critical regions of the disease. Another chromosome region harboring the disease gene may exist in the new Chinese family.

Infantile seizures and other epileptic phenotypes in a Chinese family with a missense mutation of KCNQ2

“…In the European families reported to date, the seizures have been mostly of a partial type, with only some patients showing a secondary generalization [3,7,8]. However, the affected members of this Chinese family manifested generalized tonic-clonic seizures similar to those previously reported for other Chinese families [10,20]. The age of onset in this family was evidently earlier than most typical BFIS, the onset of which is generally around 6 months.…”

“…To date, BFIS has been mapped to at least three different chromosomal segments, 19q12-13.1, 2q24, and 16p12-q12, which strongly suggests that it is a genetically heterogeneous disorder [11]. However, linkage analysis performed in several Chinese families with BFIS were negative for these three loci for typical BFIS [10,18,20], indicating that the disease gene for Chinese BFIS patients may be in another chromosome region outside the accepted established critical regions.…”

Mutation Analysis of WASF2 and GALE Genes in One Chinese Family with Benign Familial Infantile Convulsions with a Novel Locus

“…8 The third linkage region is located on chromosome 2q24, between markers D2S399 and D2S2330, in a region of 1.3 Mbps. 9 However, linkage analysis performed in several Chinese families with BFIC were negative for these three loci, 10,11 indicating that the disease gene for Chinese BFIC patients may be in another chromosome region outside the accepted established critical regions. Wang and colleagues performed a linkage analysis at the BFIC locus of 19q and screened linkage analysis at other epileptic syndrome loci.…”

Voltage-Gated Channels as Causative Agents for Epilepsies

“…Seizures in some affected individuals also occurred during a febrile episode, but most of these events were found to persist beyond the age of 6 years, which is the commonly used diagnostic cut-off for the clinical syndrome classified as febrile seizures. In febrile seizures, 90% of cases show seizures in the first 3 months of life and less than 10% develop afebrile seizures at a later age [4] A new candidate sodium channel gene for epilepsy was also proposed after the discovery that it is selectively expressed in the limbic system of the brain, giving new meaning to the term 'positional cloning'. The mRNA for sodium channel SCN5A gene, which is localized to chromosome 3p24, was expressed in the brain piriform cortex and amygdala using in situ hybridization and PCR techniques.…”

“…The genetic basis for two idiopathic epilepsies has now been pinpointed to specific ion channel proteins for two different potassium-channel genes (KCNQ2, MIM 602235 and KCNQ3, MIM 602232) [2,3] or sodium channel subunits (SCN2A, OMIM 601219) [4][5][6] . Voltages gated Channels are membranous structures formed by aggregated proteins and contain aqueous central pores that allow the passage of ions.…”