Search results for "ML"

162P Prevalence and spectrum analysis of germline BRCA1 and BRCA2 variants of unclear significance in HBOC Syndrome: Decoding the mysterious signals …

2021

Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development

2018

AbstractDe novo germline mutations in the RNA helicase DDX3X account for 1-3% of unexplained intellectual disability (ID) cases in females, and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here we use human and mouse genetics, and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development. We report the largest clinical cohort to date with DDX3X mutations (n=78), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcomes.…

Megalencephaly Syndromes and Activating Mutations in the PI3K-AKT Pathway: MPPH and MCAP

2013

The megalencephaly‐polymicrogyria‐polydactyly‐hydrocephalus (MPPH) and megalencephaly‐capillary malformation (MCAP) syndromes are highly recognizable and partly overlapping disorders of brain overgrowth (megalencephaly). Both syndromes are characterized by congenital or early postnatal megalencephaly, with a high risk for progressive ventriculomegaly leading to hydrocephalus and cerebellar tonsillar ectopia leading to Chiari malformation, and cortical brain abnormalities, specifically polymicrogyria. MCAP is further characterized by distinct cutaneous capillary malformations, finger or toe syndactyly, postaxial polydactyly, variable connective tissue dysplasia and mild focal or segmental bo…

Detection of a novel germline mutation in the von Hippel-Lindau tumour-suppressor gene by fluorescence-labelled base excision sequence scanning (F-BE…

1999

The von Hippel Lindau (VHL) syndrome is an inherited multi-tumour disorder characterised by clinical heterogeneity and high penetrance. The VHL gene has been shown to be a tumour-suppressor gene. A carrier of a germline mutation will be predisposed to a high variety of benign and malign tumours affecting different organ systems. As treatment of VHL malformations in presymptomatic stages will improve significantly the clinical outcome and the patient's quality of life, early and unambiguous detection of a germline mutation is mandatory. Direct sequencing especially of large genes might be laborious and time consuming. Therefore, most laboratories apply single strand conformational polymorphi…

Piwi proteins and piRNAs in mammalian oocytes and early embryos: From sample to sequence

2015

AbstractThe role of the Piwi/piRNA pathway during mammalian oogenesis has remained enigmatic thus far, especially since experiments with Piwi knockout mice did not reveal any phenotypic defects in female individuals. This is in striking contrast with results obtained from other species including flies and zebrafish. In mouse oocytes, however, only low levels of piRNAs are found and they are not required for their function. We recently demonstrated dynamic expression of PIWIL1, PIWIL2, and PIWIL3 during mammalian oogenesis and early embryogenesis. In addition, small RNA analysis of human, crab-eating macaque and cattle revealed that piRNAs are also expressed in the female germline and closel…

SNVSniffer: An integrated caller for germline and somatic SNVs based on Bayesian models

2015

The discovery of single nucleotide variants (SNVs) from next-generation sequencing (NGS) data typically works by aligning reads to a given genome and then creating an alignment map to interpret the presence of SNVs. Various approaches have been developed to call whether germline SNVs (or SNPs) in normal cells or somatic SNVs in cancer/tumor cells. Nonetheless, efficient callers for both germline and somatic SNVs have not yet been extensively investigated. In this paper, we present SNVSniffer, an integrated caller for germline and somatic SNVs from NGS data based on Bayesian probabilistic models. In SNVSniffer, our germline SNV calling models allele counts per site as a multinomial condition…

Germline JAK2 L611S mutation in a child with thrombocytosis

2018

Conserved and ubiquitous expression of piRNAs and PIWI genes in mollusks antedates the origin of somatic PIWI/piRNA expression to the root of bilater…

2018

AbstractPIWI proteins and a specific class of small non-coding RNAs, termed Piwi interacting RNAs (piRNAs), suppress transposon activity in animals on the transcriptional and post-transcriptional level, thus protecting genomes from detrimental insertion mutagenesis. While in vertebrates the PIWI/piRNA system appears to be restricted to the germline, somatic expression of piRNAs directed against transposons is widespread in arthropods, likely representing the ancestral state for this phylum. Here, we show that somatic expression of PIWI genes and piRNAs directed against transposons is conserved in mollusks, suggesting that somatic PIWI/piRNA expression was already realized in an early bilate…

Klar – klärer – am klärsten? Umlaut comparison as a doubtful case in contemporary German

2017

Abstract The present paper addresses doubtful cases concerning the use of umlaut in the adjectival comparison of contemporary German: bang ‘anxious’ - banger/bänger - am bangsten/ bängsten. It aims to shed light on the concrete distribution of this variation, i.e. the preference for one of the variants. Corpus-based analyses will show that the adjectives under discussion are not equally affected by umlaut variation: some are (surprisingly) stable (e.g., gesund ‘healthy’), whereas many others have a clear preference (i.e. > 70%) for non-umlauting forms (e.g., blass ‘pale’, nass ‘wet’). Interestingly, a few of the supposedly stable cases appear to have at least some non-umlauting forms (e.…

Trends in excellent self-rated health among adolescents: A comparative Nordic study

2019

Abstract Background: Excellent self-rated health (SRH) can be seen as an important component of positive health among adolescents. The aim of this paper is to examine time trends of excellent health among adolescents in five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) between 2002 and 2014, including differences between countries, gender and age. Methods: Nordic data from the Health Behaviour in School-aged Children (HBSC) survey (including 11-, 13- and 15-year-olds) from 2002 (n = 19,009), 2006 (n = 29,656), 2010 (n = 33,232) and 2014 (n = 31,540) were analysed by design-adjusted binomial logistic regression models. Results: The trend analysis of excellent SRH for Nordi…