Hereditary febrile seizures: Phenotype and evidence for a chromosome 19p locus

Kugler, Steven L.; Stenroos, Edward S.; Mandelbaum, David E.; Lehner, Thomas; McKoy, Vershon V.; Prossick, Trisha; Sasvari, Jennifer; Swannick, Krystine; Katz, Jordan; Johnson, William G.

doi:10.1002/(sici)1096-8628(19981012)79:5<354::aid-ajmg5>3.0.co;2-j

Cited by 52 publications

(23 citation statements)

References 25 publications

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“…Because the febrile seizure is the most commonly provoked seizure afflicting infants and children, it is likely that numerous factors contribute to generate heterogeneous seizure phenotypes. Actually, several loci are known to be responsible for FS (5)(6)(7)(8)(9). The febrile seizures of mother and maternal aunt may therefore most probably be accounted for by defects in other genes.…”

Section: Discussionmentioning

confidence: 99%

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A missense mutation of the Na ⁺ channel α _II subunit gene Na _v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

Sugawara

Tsurubuchi

Agarwala

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

359

186

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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...

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Section: Discussionmentioning

confidence: 99%

“…Extensive genetic studies have demonstrated that four loci are responsible for FS: FEB1 at chromosome 8q13-q21; FEB2, 19p; FEB3, 2q23-24; and FEB4, 5q14-q15 (5)(6)(7)(8)(9). A small population of individuals with FS has additional generalized epilepsy (1) or afebrile seizures.…”

Section: Generalized Epilepsy With Febrile Seizures Plus (Gefs؉) a Cmentioning

confidence: 99%

A missense mutation of the Na ⁺ channel α _II subunit gene Na _v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

Sugawara

Tsurubuchi

Agarwala

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

359

186

View full text Add to dashboard Cite

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“…But linkage analysis identiWed seven chromosomal loci for FS: FEB1 on chromosome 8q13-q21 (Wallace et al 1996), FEB2 on 19p13.3 (Johnson et al 1998Kugler et al 1998), FEB3 on 2q23-q24 (PeiVer et al 1999, FEB4 on 5q14-q15 (Nakayama et al 2000), FEB5 on 6q22-q24 (Nabbout et al 2002), FEB6 on 18p11.2 (Nakayama and Arinami 2006), and FEB7 on 21q22 (Hedera et al 2006). The IMPA2 gene was suggested as the FEB6 gene.…”

Section: Introductionmentioning

confidence: 99%

A novel genetic locus for familial febrile seizures and epilepsy on chromosome 3q26.2–q26.33

et al. 2008

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Febrile seizures (FS) are common in children, and the incidence is 2-5% before the age of 5 years. A four-generation Chinese family with autosomal dominant febrile seizure and epilepsy was studied by genome-wide linkage analysis. Significant linkage was identified with markers on chromosome 3q26.2-26.33 with a maximum pairwise LOD score of >3.00. Fine mapping defined the new genetic locus within a 10.7-Mb region between markers D3S3656 and D3S1232. A maximum multipoint LOD score of 5.27 was detected at marker D3S1565. A previously reported CLCN2 gene for epilepsy was excluded as the disease-causing gene in the family by mutational analysis of all exons and exon-intron boundaries of CLCN2 and by haplotype analysis. Mutation analysis of KCNMB2 and KCNMB3, which were two potassium-channel genes in this linkage region, did not reveal a disease causing mutation. Our results identified another novel locus on chromosome 3q26.2-26.33, and future studies of the candidate genes at the locus will identify a new gene for combined FS and idiopathic epilepsies.

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“…Segregation analysis suggested a polygenic model in families of probands with a single febrile seizure, while in families with repeated episodes of FS, inheritance best fitted autosomal dominance with reduced disease penetrance (Rich et al 1987;Johnson et al 1996). Linkage analysis studies identified five chromosomal loci for FS: FEB1 at 8q13-q21, FEB2 at 19p, FEB3 at 2q23-q24, FEB4 at 5q14-q15 and FEB5 at 6q22-q24 (Wallace et al 1996;Johnson et al 1998;Kugler et al 1998;Peiffer et al 1999;Nakayama et al 2000;Nabbout et al 2002). In some families, FS is present as part of a broader phenotypic spectrum that also includes atypical febrile seizures (FS+) and afebrile generalized and partial seizures i.e.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation

et al. 2005

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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.

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Hereditary febrile seizures: Phenotype and evidence for a chromosome 19p locus

Cited by 52 publications

References 25 publications

A missense mutation of the Na ⁺ channel α _II subunit gene Na _v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

A missense mutation of the Na ⁺ channel α _II subunit gene Na _v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

A novel genetic locus for familial febrile seizures and epilepsy on chromosome 3q26.2–q26.33

Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation

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Hereditary febrile seizures: Phenotype and evidence for a chromosome 19p locus

Cited by 52 publications

References 25 publications

A missense mutation of the Na + channel α II subunit gene Na v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

A missense mutation of the Na + channel α II subunit gene Na v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

A novel genetic locus for familial febrile seizures and epilepsy on chromosome 3q26.2–q26.33

Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation

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A missense mutation of the Na ⁺ channel α _II subunit gene Na _v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction

A missense mutation of the Na ⁺ channel α _II subunit gene Na _v 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction