RESUMEN
Synaptopathies constitute a group of neurological diseases including autism spectrum disorders (ASD) and intellectual disability (ID). They have been associated with mutations in genes encoding proteins important for the formation and stabilization of synapses, such as SHANK1-3. Loss-of-function mutations in the SHANK genes have been identified in individuals with ASD and ID suggesting that other factors modify the neurological phenotype. We report a boy with severe ID, behavioral anomalies, and language impairment who carries a balanced de novo triple translocation 46,XY,t(11;17;19)(q13.3;q25.1;q13.42). The 11q13.3 breakpoint was found to disrupt the SHANK2 gene. The patient also carries copy number variations at 15q13.3 and 10q22.11 encompassing ARHGAP11B and two synaptic genes. The CHRNA7 gene encoding α7-nicotinic acetylcholine receptor subunit and the GPRIN2 gene encoding G-protein-regulated inducer of neurite growth 2 were duplicated. Co-occurrence of a de novo SHANK2 mutation and a CHRNA7 duplication in two reported patients with ASD and ID as well as in the patient with t(11;17;19), severe ID and behavior problems suggests convergence of these genes on a common synaptic pathway. Our results strengthen the oligogenic inheritance model and highlight the presence of a large effect mutation and modifier genes collectively determining phenotypic expression of the synaptopathy.
Asunto(s)
Epistasis Genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Proteínas del Tejido Nervioso/genética , Fenotipo , Receptor Nicotínico de Acetilcolina alfa 7/genética , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Facies , Estudios de Asociación Genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Translocación GenéticaRESUMEN
We have performed single-atom magnetization curve (SAMC) measurements and inelastic scanning tunneling spectroscopy (ISTS) on individual Fe atoms on a Cu(111) surface. The SAMCs show a broad distribution of magnetic moments with 3.5 µB being the mean value. ISTS reveals a magnetization excitation with a lifetime of 200 fsec which decreases by a factor of 2 upon application of a magnetic field of 12 T. The experimental observations are quantitatively explained by the decay of the magnetization excitation into Stoner modes of the itinerant electron system as shown by newly developed theoretical modeling.