RESUMEN
Birk Barel syndrome also known as KCNK9 imprinting syndrome is a rare developmental disorder associated with a loss-of-function variant in KCNK9, an imprinted gene with maternal expression on the 8th chromosome encoding the TASK3 (TWIK-related acidity inhibited K + -channel 3). Only two variants of KCNK9 have been associated with this condition before, both of them leading to the same amino-acid exchange p.Gly236Arg (Barel, 2008, Graham, 2016). We describe a case of a 17-year-old girl presenting with very similar phenotype and pure motor neuropathy with a novel variant c.710Câ¯>â¯A: p.Ala237Asp (NM_001282534.1) in KCNK9 found by whole exome sequencing. Our case suggests that Birk Barel syndrome may not be caused only by variants leading to amino-acid exchange p.Gly236Arg but also by other missense variant in this gene and that peripheral motor neuropathy might be a feature of this syndrome.
Asunto(s)
Anomalías Craneofaciales/genética , Predisposición Genética a la Enfermedad , Impresión Genómica/genética , Discapacidad Intelectual/genética , Hipotonía Muscular/genética , Canales de Potasio de Dominio Poro en Tándem/genética , Adolescente , Secuencia de Aminoácidos/genética , Anomalías Craneofaciales/patología , Femenino , Humanos , Discapacidad Intelectual/patología , Masculino , Hipotonía Muscular/patología , Mutación Missense/genética , Secuenciación del ExomaRESUMEN
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.