Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations

• Authors: Marzieh Khani, University of Tehran; Hosein Shamshiri, Tehran University of Medical Sciences; Farzad Fatehi, Tehran University of Medical Sciences; Mohammad Rohani, Iran University of Medical Sciences; Bahram Haghi Ashtiani, Iran University of Medical Sciences; Fahimeh Haji Akhoundi, Iran University of Medical Sciences; Afagh Alavi, University of Social Welfare and Rehabilitation Sciences, Tehran; Hamidreza Moazzeni, University of Tehran; Hanieh Taheri, University of Tehran; Mina Tolou Ghani, University of Tehran; Leila Javanparast, University of Social Welfare and Rehabilitation Sciences, Tehran; Seyyed Saleh Hashemi, University of Social Welfare and Rehabilitation Sciences, Tehran; Ramona Haji-Seyed-Javadi, Emory University; Matineh Heidari, Iran University of Medical Sciences; Shahriar Nafissi, Tehran University of Medical Sciences; Elahe Elahi, University of Tehran
• Journal Title: Molecular Genetics & Genomic Medicine
• Volume: Volume 8, Number 7
• Publisher: Wiley Open Access | 2020-07-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1002/mgg3.1240
• Subjects: Biology, Genetics; Biology, Neuroscience; Health Sciences, Radiology
• Keywords: ALS; ARHSP; autosomal recessive hereditary spastic paraplegia,; juvenile amyotrophic lateral sclerosis; SPG11

Abstract

Background SPG11 mutations can cause autosomal recessive hereditary spastic paraplegia (ARHSP) and juvenile amyotrophic lateral sclerosis (JALS). Because these diseases share some clinical presentations and both can be caused by SPG11 mutations, it was considered that definitive diagnosis may not be straight forward. Methods The DNAs of referred ARHSP and JALS patients were exome sequenced. Clinical data of patients with SPG11 mutations were gathered by interviews and neurological examinations including electrodiagnosis (EDX) and magnetic resonance imaging (MRI). Results Eight probands with SPG11 mutations were identified. Two mutations are novel. Among seven Iranian probands, six carried the p.Glu1026Argfs*4‐causing mutation. All eight patients had features known to be present in both ARHSP and JALS. Additionally and surprisingly, presence of both thin corpus callosum (TCC) on MRI and motor neuronopathy were also observed in seven patients. These presentations are, respectively, key suggestive features of ARHSP and JALS. Conclusion We suggest that rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description of seven patients studied. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with SPG11 mutations are suggested. The importance of performing both EDX and MRI is emphasized. Initial screening for p.Glu1026Argfs*4 may facilitate SPG11 screenings in Iranian patients.