Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Two novel mutations in ALDH18A1 and SPG11 genes found by whole-exome sequencing in spastic paraplegia disease patients in Iran

  • Komachali, Sajad Rafiee (Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences) ;
  • Siahpoosh, Zakieh (Department of Biology, Faculty of Science, University of Sistan and Baluchestan) ;
  • Salehi, Mansoor (Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences)
  • Received : 2022.05.03
  • Accepted : 2022.08.16
  • Published : 2022.09.30
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Abstract

Hereditary spastic paraplegia is a not common inherited neurological disorder with heterogeneous clinical expressions. ALDH18A1 (located on 10q24.1) gene-related spastic paraplegias (SPG9A and SPG9B) are rare metabolic disorders caused by dominant and recessive mutations that have been found recently. Autosomal recessive hereditary spastic paraplegia is a common and clinical type of familial spastic paraplegia linked to the SPG11 locus (locates on 15q21.1). There are different symptoms of spastic paraplegia, such as muscle atrophy, moderate mental retardation, short stature, balance problem, and lower limb weakness. Our first proband involves a 45 years old man and our second proband involves a 20 years old woman both are affected by spastic paraplegia disease. Genomic DNA was extracted from the peripheral blood of the patients, their parents, and their siblings using a filter-based methodology and quantified and used for molecular analysis and sequencing. Sequencing libraries were generated using Agilent SureSelect Human All ExonV7 kit, and the qualified libraries are fed into NovaSeq 6000 Illumina sequencers. Sanger sequencing was performed by an ABI prism 3730 sequencer. Here, for the first time, we report two cases, the first one which contains likely pathogenic NM_002860: c.475C>T: p.R159X mutation of the ALDH18A1 and the second one has likely pathogenic NM_001160227.2: c.5454dupA: p.Glu1819Argfs Ter11 mutation of the SPG11 gene and also was identified by the whole-exome sequencing and confirmed by Sanger sequencing. Our aim with this study was to confirm that these two novel variants are direct causes of spastic paraplegia.

Keywords

Acknowledgement

All sources of funding for the research reported in all parts as the design of the study and collection, analysis, and interpretation of data and in writing the manuscript is by the Genome Laboratory of Isfahan, Iran. The authors would like to thank the participants and the Genome Laboratory of Isfahan.

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