Naoko Ishihara

UBA1 is an E1 ubiquitin-activating enzyme that initiates the ubiquitylation of target proteins and is thus a key component of the ubiquitin signaling pathway. Three disorders are associated with pathogenic variants of the UBA1 gene: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, lung cancer in never smokers (LCINS), and X-linked spinal muscular atrophy (XL-SMA, SMAX2). We here report a case of infantile respiratory distress syndrome followed by continuing neuromuscular symptoms. We identified a de novo hemizygous mutation, c.1660 C > T (p.Pro554Ser), in exon 15 of the UBA1 gene in this baby. This missense mutation was located with the AAD (active adenylation domain) of the protein, a known hotspot of SMAX2 mutations. This case lends support to the genotype-phenotype correlation regarding the UBA1 mutation and its related diseases.

7歳男児。体育の授業中に足を滑らせて顔面から転倒し、2時間後に眩暈・頭痛・嘔吐が出現した。近医を受診し、頭部MRIで左小脳半球に脳梗塞が認められた。発症3ヵ月後に施行されたフォロー目的のMRIで右頭頂葉と右小脳半球に小梗塞を認められ、精査目的で当院に紹介された。脳血管造影で、頸部の右捻転により左椎骨動脈が狭窄する所見と内膜の解離所見を認め、Bow hunter症候群による椎骨動脈解離および多発性脳梗塞と診断した。解離部とその近位の左椎骨動脈のコイル塞栓術を行い、術後4ヵ月の現在まで脳梗塞の再発は認めていない。

BACKGROUND: We aimed to investigate electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) findings to elucidate the interictal epileptiform discharge (IED)-related functional alterations in deep brain structures as well as the neocortex in childhood epilepsy with centrotemporal spikes (CECTS). METHODS: Ten children with CECTS (median age; 8.2 years) referred to our hospital within a year of onset were eligible for inclusion. They underwent EEG-fMRI recording during sleep. In addition, longitudinal evaluations, including medical examinations, intelligence tests, and questionnaires about developmental disabilities, were performed. The initial evaluation was performed at the same time as the EEG-fMRI, and the second evaluation was performed over 2 years after the initial evaluation. RESULTS: Three children were unable to maintain sleep during the EEG-fMRI recording, and the remaining seven children were eligible for further assessment. All patients showed unilateral-dominant centrotemporal spikes during scans. One patient had only positive hemodynamic responses, while the others had both positive and negative hemodynamic responses. All patients showed IED-related hemodynamic responses in the bilateral neocortex. For deep brain structures, IED-related hemodynamic responses were observed in the cingulate gyrus (n=4), basal ganglia (n=3), thalamus (n=2), and default mode network (n=1). Seizure frequencies at the second evaluation were infrequent or absent, and the longitudinal results of intelligence tests and questionnaires were within normal ranges. CONCLUSIONS: We demonstrated that IEDs affect broad brain areas, including deep brain structures such as cingulate gyrus, basal ganglia, and thalamus. Deep brain structures may play an important role in the pathophysiology of CECTS.