DNA methylation changes associated with cannabis use and verbal learning performance in adolescents: an exploratory whole genome methylation study.

The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders.

Genetic and genomic studies of pathogenic EXOSC2 mutations in the newly described disease SHRF implicate the autophagy pathway in disease pathogenesis.

Missense mutations in the RNA exosome component exosome component 2 (EXOSC2), also known as ribosomal RNA-processing protein 4 (RRP4), were recently identified in two unrelated families with a novel syndrome known as Short stature, Hearing loss, Retinitis pigmentosa and distinctive Facies (SHRF, #OMIM 617763). Little is known about the mechanism of the SHRF pathogenesis. Here we have studied the effect of mutations in EXOSC2/RRP4 in patient-derived lymphoblasts, clustered regularly interspaced short palindromic repeats (CRISPR)-generated mutant fetal keratinocytes and Drosophila.

-related intellectual disability syndrome: a recognisable entity.

Background: Mutations in forkhead box protein P1 () cause intellectual disability (ID) and specific language impairment (SLI), with or without autistic features (MIM: 613670). Despite multiple case reports no specific phenotype emerged so far.

Methods: We correlate clinical and molecular data of 25 novel and 23 previously reported patients with defects.

Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

Objective: The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome.

Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer.

The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription). In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC) predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense), all absent or very rare in the ExAC database.

Diagnostic approach to microcephaly in childhood: a two-center study and review of the literature.

Aim: The aim of this study was to assess the diagnostic approach to microcephaly in childhood and to identify the prevalence of the various underlying causes/disease entities.

Method: We conducted a retrospective study on a cohort of 680 children with microcephaly (399 males, 281 females; mean age at presentation 7-8mo, range 1mo-5y) from patients presenting to Charité - University Medicine Berlin (n=474) and University Hospital Dresden (n=206). Patient discharge letters were searched electronically to identify cases of microcephaly, and then the medical records of these patients were used to analyze parameters for distribution.