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サイトウ カヨコ
Saito Kayoko
齋藤 加代子 所属 医学部 医学科（東京女子医科大学病院） 職種 特任教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Phenotypes of SMA patients retaining SMN1 with intragenic mutation. |
| 掲載誌名 | 正式名：Brain & development 略 称：Brain Dev ISSNコード：18727131/03877604 |
| 掲載区分 | 国外 |
| 巻・号・頁 | pp.10.1016/j.braindev.2021.03.006 |
| 著者・共著者 | Wijaya Yogik Onky Silvana, Är Rochmah Mawaddah, Niba Emma Tabe Eko, Morisada Naoya, Noguchi Yoriko, Hidaka Yasufumi, Ozasa Shiro, Inoue Takeshi, Shimazu Tomoyuki, Takahashi Yuya, Tozawa Takenori, Chiyonobu Tomohiro, Inoue Takushi, Shiroshita Tomoyoshi, Yokoyama Atsushi, Okamoto Kentaro, Awano Hiroyuki, Takeshima Yasuhiro, Saito Toshio, Saito Kayoko, Nishio Hisahide, Shinohara Masakazu |
| 発行年月 | 2021/04 |
| 概要 | BACKGROUND:Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous deletion or intragenic mutation of the SMN1 gene. It is well-known that high copy number of its homologous gene, SMN2, modifies the phenotype of SMN1-deleted patients. However, in the patients with intragenic SMN1 mutation, the relationship between phenotype and SMN2 copy number remains unclear.METHODS:We have analyzed a total of 515 Japanese patients with SMA-like symptoms (delayed developmental milestones, respiratory failures, muscle weakness etc.) from 1996 to 2019. SMN1 and SMN2 copy numbers were determined by quantitative polymerase chain reaction (PCR) method and/or multiplex ligation-dependent probe amplification (MLPA) method. Intragenic SMN1 mutations were identified through DNA and RNA analysis of the fresh blood samples.RESULTS:A total of 241 patients were diagnosed as having SMA. The majority of SMA patients showed complete loss of SMN1 (n = 228, 95%), but some patients retained SMN1 and carried an intragenic mutation in the retaining SMN1 (n = 13, 5%). Ten different mutations were identified in these 13 patients, consisting of missense, nonsense, frameshift and splicing defect-causing mutations. The ten mutations were c.275G > C (p.Trp92Ser), c.819_820insT (p.Thr274Tyrfs*32), c.830A > G (p.Tyr277Cys), c.5C > T (p.Ala2Val), c.826 T > C (p.Tyr276His), c.79C > T (p.Gln27*), c.188C > A (p.Ser63*), c.422 T > C (p.Leu141Pro), c.835-2A > G (exon 7 skipping) and c.835-3C > A (exon 7 skipping). It should be noted here that some patients with milder phenotype carried only a single SMN2 copy (n = 3), while other patients with severe phenotype carried 3 SMN2 copies (n = 4).CONCLUSION:Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers. |
| DOI | 10.1016/j.braindev.2021.03.006 |
| PMID | 33892995 |