Emma Tabe Eko Niba1, Hisahide Nishio2, Yogik Onky Silvana Wijaya3, Poh San Lai4, Takenori Tozawa5, Tomohiro Chiyonobu6, Misaki Yamadera7, Kentaro Okamoto8, Hiroyuki Awano9, Yasuhiro Takeshima10, Toshio Saito11, Masakazu Shinohara12. 1. Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: niba@med.kobe-u.ac.jp. 2. Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan; Faculty of Medical Rehabilitation, Kobe Gakuin University, Kobe, Japan. Electronic address: nishio@reha.kobegakuin.ac.jp. 3. Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: yogik.onky@gmail.com. 4. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: poh_san_lai@nuhs.edu.sg. 5. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: takenori@koto.kpu-m.ac.jp. 6. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: chiyono@koto.kpu-m.ac.jp. 7. Department of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan. Electronic address: yamadera.misaki.gj@mail.hosp.go.jp. 8. Department of Pediatrics, Ehime Prefectural Imabari Hospital, Ehime, Japan. Electronic address: kentaro206@gmail.com. 9. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: awahiro@med.kobe-u.ac.jp. 10. Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Japan. Electronic address: ytake@hyo-med.ac.jp. 11. Department of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan. Electronic address: saito.toshio.cq@mail.hosp.go.jp. 12. Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: mashino@med.kobe-u.ac.jp.
Abstract
BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion of SMN1 exons 7 and 8. However, exon 8 is retained in some cases, where SMN2 exon 7 recombines with SMN1 exon 8, forming a hybrid SMN gene. It remains unknown how the hybrid SMN gene contribute to the SMA phenotype. METHOD: We analyzed 515 patients with clinical suspicion for SMA. SMN1 exons 7 and 8 deletion was detected by PCR followed by enzyme digestion. Hybrid SMN genes were further analyzed by nucleotide sequencing. SMN2 copy number was determined by real-time PCR. RESULTS: SMN1 exon 7 was deleted in 228 out of 515 patients, and SMN1 exon 8 was also deleted in 204 out of the 228 patients. The remaining 24 patients were judged to carry a hybrid SMN gene. In the patients with SMN1 exon 7 deletion, the frequency of the severe phenotype was significantly lower in the patients with hybrid SMN gene than in the patients without hybrid SMN gene. However, as for the distribution of SMN2 exon 7 copy number among the clinical phenotypes, there was no significant difference between both groups of SMA patients with or without hybrid SMN gene. CONCLUSION: Hybrid SMN genes are not rare in Japanese SMA patients, and it appears to be associated with a less severe phenotype. The phenotype of patients with hybrid SMN gene was determined by the copy number of SMN2 exon 7, as similarly for the patients without hybrid SMN gene.
BACKGROUND:Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion of SMN1 exons 7 and 8. However, exon 8 is retained in some cases, where SMN2 exon 7 recombines with SMN1 exon 8, forming a hybrid SMN gene. It remains unknown how the hybrid SMN gene contribute to the SMA phenotype. METHOD: We analyzed 515 patients with clinical suspicion for SMA. SMN1 exons 7 and 8 deletion was detected by PCR followed by enzyme digestion. Hybrid SMN genes were further analyzed by nucleotide sequencing. SMN2 copy number was determined by real-time PCR. RESULTS:SMN1 exon 7 was deleted in 228 out of 515 patients, and SMN1 exon 8 was also deleted in 204 out of the 228 patients. The remaining 24 patients were judged to carry a hybrid SMN gene. In the patients with SMN1 exon 7 deletion, the frequency of the severe phenotype was significantly lower in the patients with hybrid SMN gene than in the patients without hybrid SMN gene. However, as for the distribution of SMN2 exon 7 copy number among the clinical phenotypes, there was no significant difference between both groups of SMA patients with or without hybrid SMN gene. CONCLUSION: Hybrid SMN genes are not rare in Japanese SMA patients, and it appears to be associated with a less severe phenotype. The phenotype of patients with hybrid SMN gene was determined by the copy number of SMN2 exon 7, as similarly for the patients without hybrid SMN gene.
Authors: John N Milligan; Laura Blasco-Pérez; Mar Costa-Roger; Marta Codina-Solà; Eduardo F Tizzano Journal: Genes (Basel) Date: 2022-09-15 Impact factor: 4.141
Authors: John N Milligan; Jessica L Larson; Stela Filipovic-Sadic; Walairat Laosinchai-Wolf; Ya-Wen Huang; Tsang-Ming Ko; Kristin M Abbott; Henny H Lemmink; Minna Toivonen; Johanna Schleutker; Caren Gentile; Vivianna M Van Deerlin; Huiping Zhu; Gary J Latham Journal: J Mol Diagn Date: 2021-03-30 Impact factor: 5.341