Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers in some spinal muscular atrophy (SMA) patients

Brain & Development
Tomoto YamamotoHisahide Nishio

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by deletion or intragenic mutation of SMN1. SMA is classified into several subtypes based on clinical severity. It has been reported that the copy number of SMN2, a highly homologous gene to SMN1, is associated with clinical severity among SMA patients with homozygous deletion of SMN1. The purpose of this study was to clarify the genotype-phenotype relationship among the patients without homozygous deletion of SMN1. We performed molecular genetic analyses of SMN1 and SMN2 in 112 Japanese patients diagnosed as having SMA based on the clinical findings. For the patients retaining SMN1, the PCR or RT-PCR products of SMN1 were sequenced to identify the mutation. Out of the 112 patients, 106 patients were homozygous for deletion of SMN1, and six patients were compound heterozygous for deletion of one SMN1 allele and intragenic mutation in the retained SMN1 allele. Four intragenic mutations were identified in the six patients: p.Ala2Val, p.Trp92Ser, p.Thr274TyrfsX32 and p.Tyr277Cys. To the best of our knowledge, all mutations except p.Trp92Ser were novel mutations which had never been previously reported. According to our observation, clinical sever...Continue Reading

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Citations

Jun 9, 2016·Pediatric Neurology·Yoriko NoguchiHisahide Nishio
Dec 3, 2014·Brain & Development·Nur Imma Fatimah HarahapHisahide Nishio
Sep 7, 2018·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Tsuyoshi OhmuraShinichi Torii
Dec 6, 2016·Human Genome Variation·Satomi YoshimotoHisahide Nishio
Oct 17, 2020·Neurology. Genetics·Rodrigo de Holanda MendonçaEdmar Zanoteli
Nov 6, 2020·Italian Journal of Pediatrics·Ruiping ZhangChunquan Cai
Oct 11, 2020·Brain & Development·Emma Tabe Eko NibaMasakazu Shinohara
Feb 4, 2021·The Application of Clinical Genetics·Melissa C KeinathThomas W Prior
Apr 25, 2021·Brain & Development·Yogik Onky Silvana WijayaMasakazu Shinohara
Jul 22, 2021·International Journal of Neonatal Screening·Tomokazu KimizuMasakazu Shinohara
Aug 28, 2021·International Journal of Molecular Sciences·Mar Costa-RogerEduardo F Tizzano

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