Acad. Sci. USA (97, 13913-13918; First Published November 28, 2000; 10.1073͞pnas.250478897), the authors note that the exponents of some entries in Table 1 were misprinted. The correct values appear below. www.pnas.org͞cgi͞doi͞10.1073͞pnas.191384698 STATISTICS, GENETICS. For the article ''Significance analysis of microarrays applied to the ionizing radiation response'' by Virginia Goss Tusher, Robert Tibshirani, and Gilbert Chu, which appeared in number 9, April 24, 2001, of Proc. Natl. Acad. Sci. USA (98, 5116-5121; First Published April 17, 2001; 10.1073͞pnas.091062498), the authors note the following: ''In our discussion of the pairwise fold change method on page 5118, we cited a paper by Ly et al., crediting them for the method. We did not mean to imply that it was deficient for the analysis of their experiments. In fact, Ly et al. incorporate (98,(6384)(6385)(6386)(6387)(6388)(6389), the authors wish to correct the position given for the amino acid that was mutated in the patient. The mutation ''R187W'' should be ''R188W. '' www.pnas.org͞cgi͞doi͞10.1073͞pnas.191390798 FEB2, 19p; FEB3, and FEB4,. A small population of individuals with FS has additional generalized epilepsy (1) or afebrile seizures. Genes for a ␤-subunit (␤1) and an ␣ I -subunit (Na v 1.1: SCN1A) (10) of the neuronal voltage-gated Na ϩ channel have been identified to be responsible for generalized epilepsy with febrile seizures plus (GEFSϩ) type 1 and 2, respectively (11, 12). However, a large number of patients with GEFSϩ still show no mutation for those genes. These, therefore, suggest that other genes might also be involved in GEFSϩ and FS associated with afebrile seizures. The chromosomal locus 2q24, in which GEFSϩ has been mapped, harbors not only Na v 1.1 but also other ␣-subunits including Na v 1.2 (SCN2A) (10,(13)(14)(15). Given that Na v 1.2 is also expressed in high levels in the central nervous system with a tissue-specific profile (16), Na v 1.2 is an intriguing candidate. In the present study, we report a mutation of Na v 1.2 found in a patient with FS and afebrile seizures. A channel harboring the mutation shows abnormal electrophysiological properties that may underlie the neuronal hyperexcitability that triggers seizure activity. Materials and MethodsPatients and Pedigrees. This study recruited nineteen unrelated Japanese families with members clinically diagnosed with GEFSϩ or febrile seizures associated with afebrile seizures. Each participating subject or a responsible adult signed an informed consent form approved by the Ethics Review Committee of Fukuoka University or similar committees of the participating institutions. The proband of family K1 is a 6-yr-old boy with normal development (Fig. 1A). He had the first febrile seizure (FS) at 8 months of age and suffered 17 episodes of FS thereafter at both high and low grade fever. The FS were generalized tonic or tonic-clonic convulsions with duration of 1-5 min per episode. Since 4 yr of age, he also has experienced brief afebrile atonic seizures 5 times. The...

Summary:Purpose: Severe myoclonic epilepsy in infancy (SMEI) is a distinct epilepsy syndrome. Patients with borderline SMEI (SMEB) are a subgroup with clinical features similar to those of core SMEI but are not necessarily consistent with the accepted diagnostic criteria for core SMEI. The aim of this study was to delineate the genetic correlation between core SMEI and SMEB and to estimate the frequency of mutations in both phenotypes.Methods: We examined 96 healthy volunteers and 58 unrelated individuals whose clinical features were consistent with either core SMEI (n = 31) or SMEB (n = 27). We screened for genetic abnormalities within exons and their flanking introns of the genes encoding major subunits of the Na + channels (SCN1A, SCN2A, SCN1B, and SCN2B) by using a direct sequencing method.Results: In both core SMEI and SMEB, various mutations of SCN1A including nonsense and missense mutations were identified, whereas no mutations of SCN2A, SCN1B, and SCN2B were found within the regions examined. All mutations were heterozygous and not found in 192 control chromosomes. Mutations were identified in 26 (44.8%) of the 58 individuals and were more frequent (p < 0.05) in core SMEI (19 of 31) than in SMEB (seven of 27), as assessed by the continuity-adjusted χ 2 test. Mutations resulting in a molecular truncation were found only in core SMEI. Among the mutations, two missense mutations were found in both core SMEI and SMEB.Conclusions: Our findings confirm that SMEB is part of the SMEI spectrum and may expand the recognition of SMEI and suggest other responsible or modifying genes. Key Words: Autosomal dominant epilepsy with febrile seizures plus (ADEFS+)-Channelopathy-GABA A receptor-Generalized epilepsy with febrile seizures plus (GEFS+)-Ion channel.

Mutations of genes encoding ␣4, ␤2, or ␣2 subunits (CHRNA4, CHRNB2, or CHRNA2, respectively) of nAChR [neuronal nicotinic ACh (acetylcholine) receptor] cause nocturnal frontal lobe epilepsy (NFLE) in human. NFLE-related seizures are seen exclusively during sleep and are characterized by three distinct seizure phenotypes: "paroxysmal arousals," "paroxysmal dystonia," and "episodic wandering." We generated transgenic rat strains that harbor a missense mutation S284L, which had been identified in CHRNA4 in NFLE. The transgenic rats were free of biological abnormalities, such as dysmorphology in the CNS, and behavioral abnormalities. The mRNA level of the transgene (mutant Chrna4) was similar to the wild type, and no distorted expression was detected in the brain. However, the transgenic rats showed epileptic seizure phenotypes during slow-wave sleep (SWS) similar to those in NFLE exhibiting three characteristic seizure phenotypes and thus fulfilled the diagnostic criteria of human NFLE. The therapeutic response of these rats to conventional antiepileptic drugs also resembled that of NFLE patients with the S284L mutation. The rats exhibited two major abnormalities in neurotransmission: (1) attenuation of synaptic and extrasynaptic GABAergic transmission and (2) abnormal glutamate release during SWS. The currently available genetically engineered animal models of epilepsy are limited to mice; thus, our transgenic rats offer another dimension to the epilepsy research field.