A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy

Shinichi Hirose, H. Iwata, H. Akiyoshi, Katsuhiro Kobayashi, M. Ito, K. Wada, S. Kaneko, A. Mitsudome

Research output: Contribution to journalArticle

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Abstract

Objective: To identify the mutation responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a nonwhite family. Background: ADNFLE is newly recognized as an entity of idiopathic partial epilepsy. Recently, two different mutations of the neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) gene were identified in a white family as a cause of ADNFLE. Methods: Four affected and three unaffected individuals in three generations of a Japanese family with ADNFLE, and 100 unrelated healthy Japanese volunteers were studied. Clinical features and EEG findings in affected individuals were consistent with those of ADNFLE reported in white families with ADNFLE. Mutations within the CHRNA4 gene were screened for using single-strand conformation polymorphism analysis (SSCA) and were determined by direct sequencing. The mutation identified was sought in volunteers by the amplification refractory mutation system. Results: A C-to-T exchange (C755T) was found in exon 5 of the CHRNA4 gene on one allele of affected individuals. C755T segregated in affected individuals and was not found in 200 alleles obtained from the volunteers. C755T replaced serine 252 (Ser252) in the second membrane-spanning domain (M2) of CHRNA4 with a leucine. Ser252 is conserved characteristically in the α-subunit of acetylcholine receptor and is considered to play an important role in channel function. Conclusion: C755T is a novel missense mutation of the CHRNA4 gene causing autosomal dominant nocturnal frontal lobe epilepsy in this Japanese family.

Original languageEnglish
Pages (from-to)1749-1753
Number of pages5
JournalNeurology
Volume53
Issue number8
Publication statusPublished - Nov 10 1999

Fingerprint

Mutation
Serine
Genes
Volunteers
Alleles
Partial Epilepsy
Nicotinic Receptors
Cholinergic Receptors
Missense Mutation
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy
Leucine
Electroencephalography
Exons
Healthy Volunteers
Membranes

Keywords

  • Autosomal dominant nocturnal frontal lobe epilepsy
  • Channelopathy
  • Epilepsy
  • Neuronal nicotinic acetylcholine receptor α4 subunit
  • Neurotransmitter
  • Nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hirose, S., Iwata, H., Akiyoshi, H., Kobayashi, K., Ito, M., Wada, K., ... Mitsudome, A. (1999). A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology, 53(8), 1749-1753.

A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. / Hirose, Shinichi; Iwata, H.; Akiyoshi, H.; Kobayashi, Katsuhiro; Ito, M.; Wada, K.; Kaneko, S.; Mitsudome, A.

In: Neurology, Vol. 53, No. 8, 10.11.1999, p. 1749-1753.

Research output: Contribution to journalArticle

Hirose, S, Iwata, H, Akiyoshi, H, Kobayashi, K, Ito, M, Wada, K, Kaneko, S & Mitsudome, A 1999, 'A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy', Neurology, vol. 53, no. 8, pp. 1749-1753.
Hirose S, Iwata H, Akiyoshi H, Kobayashi K, Ito M, Wada K et al. A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology. 1999 Nov 10;53(8):1749-1753.
Hirose, Shinichi ; Iwata, H. ; Akiyoshi, H. ; Kobayashi, Katsuhiro ; Ito, M. ; Wada, K. ; Kaneko, S. ; Mitsudome, A. / A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. In: Neurology. 1999 ; Vol. 53, No. 8. pp. 1749-1753.
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AU - Ito, M.

AU - Wada, K.

AU - Kaneko, S.

AU - Mitsudome, A.

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N2 - Objective: To identify the mutation responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a nonwhite family. Background: ADNFLE is newly recognized as an entity of idiopathic partial epilepsy. Recently, two different mutations of the neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) gene were identified in a white family as a cause of ADNFLE. Methods: Four affected and three unaffected individuals in three generations of a Japanese family with ADNFLE, and 100 unrelated healthy Japanese volunteers were studied. Clinical features and EEG findings in affected individuals were consistent with those of ADNFLE reported in white families with ADNFLE. Mutations within the CHRNA4 gene were screened for using single-strand conformation polymorphism analysis (SSCA) and were determined by direct sequencing. The mutation identified was sought in volunteers by the amplification refractory mutation system. Results: A C-to-T exchange (C755T) was found in exon 5 of the CHRNA4 gene on one allele of affected individuals. C755T segregated in affected individuals and was not found in 200 alleles obtained from the volunteers. C755T replaced serine 252 (Ser252) in the second membrane-spanning domain (M2) of CHRNA4 with a leucine. Ser252 is conserved characteristically in the α-subunit of acetylcholine receptor and is considered to play an important role in channel function. Conclusion: C755T is a novel missense mutation of the CHRNA4 gene causing autosomal dominant nocturnal frontal lobe epilepsy in this Japanese family.

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