UBR5 Gene Mutation Is Associated with Familial Adult Myoclonic Epilepsy in a Japanese Family

Takeo Kato,Tomohiro Nakamura,Gen Tamiya,Toru Kawanami,Shigeki Arawaka,Satoshi Makino,Ikuo Tooyama,Shingo Koyama

doi:10.5402/2012/508308

Takeo Kato, Tomohiro Nakamura + Show 6 more

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https://doi.org/10.5402/2012/508308

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Abstract

The causal gene(s) for familial adult myoclonic epilepsy (FAME) remains undetermined. To identify it, an exome analysis was performed for the proband in a Japanese FAME family. Of the 383 missense/nonsense variants examined, only c.5720G>A mutation (p.Arg1907His) in the UBR5 gene was found in all of the affected individuals in the family, but not in the nonaffected members. Such mutation was not found in any of the 85 healthy individuals in the same community nor in any of the 24 individuals of various ethnicities. The present study demonstrated an FAME-associated mutation in the UBR5 gene, which is located close to the reported locus linked to Japanese FAME families.

Highlights

Familial adult myoclonic epilepsy (FAME), or benign adult familial myoclonic epilepsy (BAFME), is a neurological disease of an autosomal-dominant inheritance, which is characterized clinically by adult onset of finger tremulous movement mixed with myoclonic jerks
We report that a mutation of the gene encoding Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) is associated with FAME in a Japanese family
Of the 467 functional variants, the probes of 383 variants were successfully designed, and the GoldenGate Assay was performed for 10 family members, consisting of 5 patients with FAME (II-4, II-5, III-1, III-4, and IV-2) and 5 nonaffected members (II-6, III-2, III-3, III-5, and IV-1) (Figure 1)

Summary

Introduction

Familial adult myoclonic epilepsy (FAME), or benign adult familial myoclonic epilepsy (BAFME), is a neurological disease of an autosomal-dominant inheritance, which is characterized clinically by adult onset of finger tremulous movement mixed with myoclonic jerks. Linkage studies have mapped FAME-associated loci to chromosome 8q23.3q24.11 in Japanese families [1, 2], to chromosome 2p11.1q12.2 in Italian [3,4,5] and Spanish [6] families, and chromosome 5p15.31-p15 in a French family [7]. The identification of the causal gene(s) for FAME is of great importance to the understanding of the molecular basis of the disease, gene(s) responsible for FAME has not been identified. We report that a mutation of the gene encoding UBR5 (ubiquitin protein ligase E3 component nrecognin 5) is associated with FAME in a Japanese family

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