A case of adult onset Sandhoff disease that mimics Brown-Vialetto-Van Laere syndrome

Khani, Marzieh; Shamshiri, Hosein; Moazzeni, Hamidreza; Taheri, Hanieh; Ahmadieh, Hamid; Alavi, Afagh; Farboodi, Niloofar; Nafissi, Shahriar; Elahi, Elahe

doi:10.1016/j.nmd.2021.03.003

Cited by 1 publication

(1 citation statement)

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“…This possibility is negated by observation of sensory indications in the MND‐227 patients and the absence of sensory indications in all forms of SMA. All in all, the clinical and genetic findings pertaining to MND‐227 patients are yet another indication of the complexities and overlaps amongst various neurological diseases [7, 50–53]. Here, these issues are imperfectly resolved by designating the name “non‐Kennedy SBMA” to the disease MND‐227.…”

Section: Discussionmentioning

confidence: 99%

Identification of UBA1 as the causative gene of an X‐linked non‐Kennedy spinal–bulbar muscular atrophy

Khani

Nafissi

Shamshiri

et al. 2022

Euro J of Neurology

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Background and purpose Spinal–bulbar muscular atrophy (SBMA) (Kennedy's disease) is a motor neuron disease. Kennedy's disease is nearly exclusively caused by mutations in the androgen receptor encoding gene (AR). The results of studies aimed at identification of the genetic cause of a disease that best approximates SBMA in a pedigree (four patients) without mutations in AR are reported. Methods Clinical investigations included thorough neurological and non‐neurological examinations and testing. Genetic analysis was performed by exome sequencing using standard protocols. UBA1 mutations were modeled on the crystal structure of UBA1. Results The clinical features of the patients are described in detail. A missense mutation in UBA1 (c.T1499C; p.Ile500Thr) was identified as the probable cause of the non‐Kennedy SBMA in the pedigree. Like AR, UBA1 is positioned on chromosome X. UBA1 is a highly conserved gene. It encodes ubiquitin‐like modifier activating enzyme 1 (UBA1) which is the major E1 enzyme of the ubiquitin–proteasome system. Interestingly, UBA1 mutations can also cause infantile‐onset X‐linked spinal muscular atrophy (XL‐SMA). The mutation identified here and the XL‐SMA causative mutations were shown to affect amino acids positioned in the vicinity of UBA1's ATP binding site and to cause structural changes. Conclusion UBA1 was identified as a novel SBMA causative gene. The gene affects protein homeostasis which is one of most important components of the pathology of neurodegeneration. The contribution of this same gene to the etiology of XL‐SMA is discussed.

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Section: Discussionmentioning

confidence: 99%