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INTRODUCTION/AIMS: Language is frequently affected in patients with sporadic amyotrophic lateral sclerosis (sALS), with reduced performance in naming, syntactic comprehension, grammatical expression, and orthographic processing. However, the language profile of patients with familial type 8 ALS (ALS8), linked to p.P56S VAPB mutation, remains unclear. We investigated language in patients with ALS8 by examining their auditory comprehension and verbal production. METHODS: We included three groups of participants: (1) patients with sALS (n = 20), (2) patients with familial ALS8 (n = 22), and (3) healthy controls (n = 21). The groups were matched for age, sex, and education level. All participants underwent a comprehensive language battery, including the Boston Diagnostic Aphasia Examination, the reduced Token test, letter fluency, categorical fluency (animals), word definition from the Cambridge Semantic Memory Research Battery, and a narrative discourse analysis. Participants also were evaluated using Addenbrooke's Cognitive Exam-Revised Version, the Hospital Anxiety and Depression Scale, and the ALS Functional Rating Scale-Revised. RESULTS: Compared to controls, sALS and ALS8 patients had impaired performance on oral (syntactic and phonological processing) comprehension and inappropriate discourse cohesion. sALS and ALS8 did not differ in any language measure. There was no correlation between language scores and functional and psychiatric scales. DISCUSSION: ALS8 patients exhibit language deficits that are independent of motor features. These findings are consistent with the current evidence suggesting that ALS8 has prominent non-motor features.
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OBJECTIVE: ANO5-related myopathy is an important cause of limb-girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. METHODS: A national cross-sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. RESULTS: Thirty-seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss-of-function variants were not associated with specific phenotypes. INTERPRETATION: We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.
