Open AccessDescription of combined ARHSP/JALS phenotype in some patients with SPG11 mutations
Author(s) -
Khani Marzieh,
Shamshiri Hosein,
Fatehi Farzad,
Rohani Mohammad,
Haghi Ashtiani Bahram,
Akhoundi Fahimeh Haji,
Alavi Afagh,
Moazzeni Hamidreza,
Taheri Hanieh,
Ghani Mina Tolou,
Javanparast Leila,
Hashemi Seyyed Saleh,
HajiSeyedJavadi Ramona,
Heidari Matineh,
Nafissi Shahriar,
Elahi Elahe
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1240
Subject(s) - proband , hereditary spastic paraplegia , medicine , mutation , tardbp , amyotrophic lateral sclerosis , magnetic resonance imaging , exome sequencing , phenotype , genetics , pathology , radiology , gene , disease , biology , sod1
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.