Genetic and phenotypic spectrum associated with IFIH1 gain-of-function

IFIH1 gain-of-function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate

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peer reviewe

L’hypothermie induite dans l'encéphalopathie anoxo-ischémique du nouveau-né

peer reviewedphysiopathologie de l'asphyxie à terme et logique des traitements par hypothermie

Lafora disease and diabete - Enlarging clinical phenotype

peer reviewe

Le potentiel des cellules souches dans l'encéphalopathie anoxo-ischémique du nouveau-né

peer reviewe

Dystonie et ataxie récurrente chez un enfant avec anticorps anti-neurochondrines

We report the case of a 7-years-old boy who developed severe recurrent episodes of ataxia. Following the persistence of intrathecal pleocytosis and oligoclonal bands, auto-immune workup was performed and anti-neurochondrin antibodies in the cerebro-spinal fluid were discovered. Other investigations returned normal, no oncologic accompaniments were found. Clinical examination identified cerebellar ataxia, cervical dystonia, choreic movements of the upper limbs, action tremor, opsoclonus, dysarthria and akathisis (Video 1). Cognitive affective cerebellar syndrome, including neuropsychological impairment associated with significant emotional lability, was also found. Initial corticosteroid therapy (intravenous methylprednisolone 30mg/kg for 3 days) resulted in significant improvement. However, following the third relapse, a long-term corticotherapy with monthly intravenous methylprednisolone 500mg/m² was initiated. After 8 months, in order to avoid side effects, this treatment was replaced by mycophenolic acid. No relapse was observed since then. The child currently keeps slightly ataxic gait as well as significant cognitive impairment. Autoimmune etiologies of movement disorders are increasingly recognized, even in children. Unexplained repeated episodes of ataxia of subacute onset may require a workup with comprehensive neural IgG screening, especially since immune therapies seem more effective than what is observed in adults