Human GABRB3 blocking peptide

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of an inverted duplication of proximal chromosome 15 [inv dup(15)] presenting as a small supernumerary marker chromosome (SSMC) at amniocentesis associated with concomitant microduplication of 8q22.1. Materials and methods: A 39-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age, and the result was 47, XY, +mar dn. The woman requested for repeat amniocentesis at 20 weeks of gestation. Array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) and DNA methylation analysis were applied to determine the nature of the SSMC. Results: aCGH on the uncultured amniocytes revealed the result of arr 8q22.1 (93,918,763 - 96,618,539) x 3.0, arr 15q11.2q13.2 (22,765,628-30,658,876) x 4.0, arr 15q13.2q13.3 (30,653,877 - 32,509,926) x 3.0 [GRCh37 (hg19)]. Interphase FISH analysis using RP11-34H12 [15q13.2; Texas Red, 30,709,033-30,893,021 (hg19)] on 100 uncultured amniocytes showed that 38 cells had three signals, 45 cells had four signals and 27 cells had two signals. The parental bloods had normal aCGH results. The karyotype of cultured amniocytes was 47, XY, +inv dup(15) (pter -> q13::q13 -> pter) which was confirmed by metaphase FISH analysis. No informative markers could be found in QF-PCR analysis. DNA methylation analysis on cord blood confirmed a maternal origin of the 15q11-q13 gene dosage increase with a result of 15q11.2 SNRPN DNA hypermethylation. Postnatal cytogenetic analysis on cord blood, umbilical cord and placenta showed the results consistent with the prenatal diagnosis. Conclusion: Molecular cytogenetic techniques are useful for rapid diagnosis of an inv dup(15) chromosome presenting as an SSMC at amniocentesis. (C) 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.

Angelman syndrome is characterised by neurodevelopmental impairment (with or without epileptic seizures) associated with functional deficit of the UBE3A gene. Different mechanisms of UBE3A inactivation correlate with clinical phenotypes of varying severity. However, three distinctive, highly consistent electroencephalographic rhythmic patterns can be observed in almost all patients irrespective of genotype, clinical severity and the presence or severity of a seizure disorder. Pattern I consists of runs of high amplitude 2-3/s rhythmic activity predominating over the frontal regions. Pattern 11 consists of more diffuse runs of 4-6/s rhythmic activity. Pattern III consists of bursts or runs of high amplitude 3-5/s rhythmic activity, maximal over the occipital region, sometimes containing small spikes and facilitated by eye closure. We review the available neurophysiological evidence from human and animal studies in the light of recent molecular advances. Electroencephalographic features in both patients and various mouse models point to two separable categories: characteristic rhythmic patterns, which are not related to epilepsy, and less specific epilepsy-related discharge activity. These features are consistent with a model of cortical and thalamo-cortical dysfunction resulting from dysregulation of synaptic GABAergic neurotransmission by (1) deficient recruitment of functional GABA(A) receptors related to reduced UBE3A gene expression in all cases and (2) decreased amount of beta3 sub-unit in these receptors related to reduced GABRB3 gene expression in deletion cases.