Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia

Atsushi Takata, Maiko Kato, Masayuki Nakamura, Takeo Yoshikawa, Shigenobu Kanba, Akira Sano, Tadafumi Kato

研究成果: ジャーナルへの寄稿学術誌査読

41 被引用数 (Scopus)

抄録

Background: Whole-exome sequencing using next-generation technologies has been previously demonstrated to be able to detect rare disease-causing variants. Progressive external ophthalmoplegia (PEO) is an inherited mitochondrial disease that follows either autosomal dominant or recessive forms of inheritance (adPEO or arPEO). AdPEO is a genetically heterogeneous disease and several genes, including POLG1 and C10orf2/Twinkle, have been identified as responsible genes. On the other hand, POLG1 was the only established gene causing arPEO with mitochondrial DNA deletions. We previously reported a case of PEO with unidentified genetic etiology. The patient was born of a first-cousin marriage. Therefore, the recessive form of inheritance was suspected.Results: To identify the disease-causing variant in this patient, we subjected the patient's DNA to whole-exome sequencing and narrowed down the candidate variants using public data and runs of homozygosity analysis. A total of 35 novel, putatively functional variants were detected in the homozygous segments. When we sorted these variants by the conservation score, a novel missense variant in RRM2B, whose heterozygous rare variant had been known to cause adPEO, was ranked at the top. The list of novel, putatively functional variants did not contain any other variant in genes encoding mitochondrial proteins registered in MitoCarta.Conclusions: Exome sequencing efficiently and effectively identified a novel, homozygous missense variant in RRM2B, which was strongly suggested to be causative for arPEO. The findings in this study indicate arPEO to be a genetically heterogeneous disorder, as is the case for adPEO.

本文言語英語
論文番号R92
ジャーナルGenome biology
12
9
DOI
出版ステータス出版済み - 9月 28 2011

!!!All Science Journal Classification (ASJC) codes

  • 生態、進化、行動および分類学
  • 遺伝学
  • 細胞生物学

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