Wijaya, Yogik Onky Silvana and Ar Rohmah, Mawaddah and Niba, Emma Tabe Eko and Morisada, Naoya and Noguchi, Yoriko and Hidaka, Yasufumi and Ozasa, Shiro and Inoue, Takeshi and Shimazu, Tomoyuki and Takahashi, Yuya and Tozawa, Takenori and Chiyonobu, Tomohiro and Inoue, Takushi and Shiroshita, Tomoyoshi and Yokoyama, Atsushi and Okamoto, Kentaro and Awano, Hiroyuki and Takeshima, Yasuhiro and Saito, Toshio and Saito, Kayoko and Nishio, Hisahide and Shinohara, Masakazu (2021) Phenotypes of SMA patients retaining SMN1 with intragenic mutation. Brain and Development, 43 (7). 745 – 758. ISSN 03877604
Full text not available from this repository. (Request a copy)Abstract
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.819820insT (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. © 2021 The Japanese Society of Child Neurology
Item Type: | Article |
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Additional Information: | Cited by: 16; All Open Access, Bronze Open Access, Green Open Access |
Uncontrolled Keywords: | Adolescent; Child; Female; Humans; Infant; Infant, Newborn; Male; Muscular Atrophy, Spinal; Mutation; Patient Acuity; Phenotype; Survival of Motor Neuron 1 Protein; Survival of Motor Neuron 2 Protein; survival motor neuron protein 1; survival motor neuron protein 2; SMN1 protein, human; SMN2 protein, human; survival motor neuron protein 1; survival motor neuron protein 2; adolescent; Article; blood sampling; child; controlled study; copy number variation; developmental delay; DNA determination; exon; female; frameshift mutation; gene mutation; human; infant; Japanese (people); major clinical study; male; methylation-specific multiplex ligation-dependent probe amplification; missense mutation; muscle weakness; newborn; nonsense mutation; phenotype; real time polymerase chain reaction; respiratory failure; RNA analysis; school child; spinal muscular atrophy; splicing defect; genetics; mutation; pathophysiology; patient acuity; phenotype; spinal muscular atrophy |
Subjects: | R Medicine > RJ Pediatrics |
Divisions: | Faculty of Medicine, Public Health and Nursing > Biomedical Sciences |
Depositing User: | Sri JUNANDI |
Date Deposited: | 27 Sep 2024 02:41 |
Last Modified: | 27 Sep 2024 02:41 |
URI: | https://ir.lib.ugm.ac.id/id/eprint/4564 |