INTRODUCTION: Neurodegenerative diseases of childhood present with progressive decline in cognitive, social, and motor function and are frequently associated with seizures in different stages of the disease. Here we report a patient with severe progressive neurodegeneration with drug-resistant epilepsy of unknown etiology from the age of 2 years. METHODS AND RESULTS: Using whole exome sequencing, we found heterozygous missense de novo variant c.628G > A (p.Glu210Lys) in the UBTF gene. This variant was recently described as de novo in 11 patients with similar neurodegeneration characterized by developmental decline initially confined to motor development followed by language regression, appearance of an extrapyramidal movement disorder, and leading to severe intellectual disability. In 3 of the 11 patients described so far, seizures were also present. CONCLUSIONS: Our report expands the complex phenotype of neurodegeneration associated with the c.628G > A variant in the UBTF gene and helps to clarify the relation between this one single recurrent pathogenic variant described in this gene to date and its phenotype. The UBTF gene should be considered a novel candidate gene in neurodegeneration with or without epilepsy.

• MeSH
• fenotyp * MeSH
• lidé MeSH
• mladiství MeSH
• mutace genetika   MeSH
• neurodegenerativní nemoci komplikace   diagnostické zobrazování   genetika   MeSH
• refrakterní epilepsie komplikace   diagnostické zobrazování   genetika   MeSH
• transkripční iniciační komplex Pol1 - proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Recently, a study providing insight into GABRB3 mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype-phenotype correlations. METHODS: The proband (twin B) was referred for massively parallel sequencing of epilepsy-related gene panel because of hypotonia and neonatal seizures. The revealed variant was confirmed with Sanger sequencing in the proband and the twin A, and both parents were tested for the presence of the variant. RESULTS: We report a case of epilepsy of infancy with migrating focal seizures (EIMFS) of neonatal onset in monozygotic twins with a de novo novel GABRB3 variant p.Thr281Ala. The variant has a uniform presentation on an identical genomic background. In addition, early seizure-onset epilepsy associated with GABRB3 mutation has been until now described only for the p.Leu256Gln variant in the GABRB3 (Møller et al 2017, Myers et al 2016) located in the transmembrane domain just as the p.Thr281Ala variant described here. CONCLUSION: De novo GABRB3 mutations may cause neonatal-onset EIMFS with early-onset hypotonia, respiratory distress, and severe developmental delay.

• MeSH
• dvojčata monozygotní genetika   MeSH
• epilepsie farmakoterapie   epidemiologie   genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mutace * MeSH
• nemoci u dvojčat farmakoterapie   epidemiologie   genetika   MeSH
• novorozenec MeSH
• receptory GABA-A genetika   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH