Pathogenic mutations identified by a multimodality approach in 117 Japanese Fanconi anemia patients
| Autor: | Tomohiro Morio, Kazuo Tamura, Jun Yasuda, Shu Tadaka, Hiroshi Kawabata, Yuichi Shiraishi, Satoru Miyano, Minoru Takata, Kengo Kinoshita, Miharu Yabe, Kenichi Yoshida, Masayuki Yamamoto, Tomoo Osumi, Keitaro Matsuo, Minako Mori, Ryoji Kobayashi, Souichi Adachi, Hiromasa Yabe, Yasushi Noguchi, Etsuro Ito, Akifumi Takaori-Kondo, Asuka Hira, Seiji Kojima, Yusuke Okuno, Hideki Muramatsu, Seishi Ogawa, Kohsuke Imai, Michiko Anmae |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Oncology medicine.medical_specialty Genome-wide association study Disease Article Japan FANCG Fanconi anemia Internal medicine hemic and lymphatic diseases medicine Humans Missense mutation Genetics business.industry Bone marrow failure Hematology medicine.disease Bone Marrow Failure Fanconi Anemia Complementation Group Proteins FANCA FANCB Fanconi Anemia Mutation Female Errata Corrige business Genome-Wide Association Study |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | Fanconi anemia is a rare recessive disease characterized by multiple congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancies. It results from mutations in one of the 22 known FANC genes. The number of Japanese Fanconi anemia patients with a defined genetic diagnosis was relatively limited. In this study, we reveal the genetic subtyping and the characteristics of mutated FANC genes in Japan and clarify the genotype-phenotype correlations. We studied 117 Japanese patients and successfully subtyped 97% of the cases. FANCA and FANCG pathogenic variants accounted for the disease in 58% and 25% of Fanconi anemia patients, respectively. We identified one FANCA and two FANCG hot spot mutations, which are found at low percentages (0.04-0.1%) in the whole-genome reference panel of 3,554 Japanese individuals (Tohoku Medical Megabank). FANCB was the third most common complementation group and only one FANCC case was identified in our series. Based on the data from the Tohoku Medical Megabank, we estimate that approximately 2.6% of Japanese are carriers of disease-causing FANC gene variants, excluding missense mutations. This is the largest series of subtyped Japanese Fanconi anemia patients to date and the results will be useful for future clinical management. |
| Databáze: | OpenAIRE |
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