by Peter Bauer  , Gabriele Wildhardt  , Dieter Gläser  , Clemens Müller-Reible  , Hanno J. Bolz  , Hanns-Georg Klein  , Ulrich Finckh  and Ute Hehr

Received: 24 September 2017;  Published: 28 April 2018;  doi: 10.21926/obm.genet.1802019

We present, on behalf of the German Society of Human Genetics, guidelines for molecular genetic diagnostics with high throughput technology, for example using Next-Generation Sequencing. This work was put together by a group of experts and included public commenting of the members of the German Society of Human Genetics. While experts appreciated the fundamental work of the EuroGentest guidelines for diagnostic next-generation sequencing, we identified a couple of new as well as country-specific topics that we have [...]

by Stanislav Birko  , Marie-Eve Lemoine  , Minh Thu Nguyen  and Vardit Ravitsky

Received: 10 February 2018;  Published: 19 April 2018;  doi: 10.21926/obm.genet.1802018

Women’s reproductive autonomy, and its translation into informed free choice regarding prenatal testing, is a dominant concept in the bioethical discourse concerning prenatal testing. This discourse is based on the premise that access to information regarding the pregnancy promotes autonomous decision-making. However, studies show that the offer of prenatal screening as a routine part of pregnancy care is not supported, to a large degree, by appropriate informed consent mechanisms. This means that the implementatio [...]

by Nagarajan Paramasivam  , Martin Granzow  , Christina Evers  , Katrin Hinderhofer  , Stefan Wiemann  , Claus R. Bartram  , Roland Eils  and Matthias Schlesner

Received: 24 October 2017;  Published: 16 April 2018;  doi: 10.21926/obm.genet.1802017

With genome sequencing entering the clinics as diagnostic tool to study genetic disorders, there is an increasing need for bioinformatics solutions that enable precise causal variant identification in a timely manner. Background: Workflows for the identification of candidate disease-causing variants perform usually the following tasks: i) identification of variants; ii) filtering of variants to remove polymorphisms and technical artifacts; and iii) prioritization of the remaining variants to provide a small set of [...]

by Eunise M. Aquino  , Miles C. Benton  , Larisa M. Haupt  , Heidi G. Sutherland  , Lyn R. Griffiths  and Rodney A. Lea

Received: 12 February 2018;  Published: 11 April 2018;  doi: 10.21926/obm.genet.1802016

DNA methylation involves the covalent transfer of a methyl group to the C-5 position of the cytosine ring on a DNA strand which can affect gene transcription. DNA methylation is both heritable and modifiable. In recent years, epigenome-wide association studies using high-throughput technologies have associated variation in DNA methylation levels with normal and pathological aging processes in human populations. Consequently, DNA methylation patterns have been used to construct epigenetic clocks which can serve as p [...]

by Tobias Geis  , Ute Hehr  , Roland Brandl  , Saskia Herbst  , Hugo Segerer  , Michael Melter  and Sophie Hinreiner

Received: 31 August 2017;  Published: 06 March 2018;  doi: 10.21926/obm.genet.1801015

Background: Neonatal muscular hypotonia is a common clinical feature on neonatal intensive care units with a broad spectrum of etiologies. Besides more common and obvious underlying conditions like prematurity or Down syndrome many rare disorders with often poor prognosis need to be considered. Congenital brain malformations detected on ultrasound or/and magnetic resonance imaging might constitute the clinical hallmark in differential diagnosis. We report on our approach combining cerebral imaging and application o [...]

by Jiani Yin  , David Oleson  and Christian P. Schaaf

Received: 31 August 2017;  Published: 24 February 2018;  doi: 10.21926/obm.genet.1801014

Autism spectrum disorder is a clinically heterogeneous condition, characterized by social deficits, language impairment, repetitive behaviors, and restricted interest. Autism displays significant genetic heterogeneity. In the past one and a half decades, next generation sequencing has enabled identification of many variants that predispose to autism. These discoveries have improved understanding of the disease etiology of autism spectrum disorder. In this review article, we will address how development of next gene [...]

by Martina C Cornel

Received: 13 July 2017;  Published: 11 February 2018;  doi: 10.21926/obm.genet.1801013

Technology makes it possible to expand many of the current screening programs. In preconception screening for carrier status of recessive diseases, prenatal screening for aneuploidies and neonatal screening initially programs were targeting one or a few conditions. Tandem mass spectrometry and genomic technologies, such as sequencing and panel testing, make it possible to increase the scope of the programs to include more disorders or markers. While inclusion of more similar conditions may lead to a better achievem [...]

by Khue Vu Nguyen

Received: 18 January 2018;  Published: 31 January 2018;  doi: 10.21926/obm.genet.1801012

With the increasing ability to control infectious and nutritional diseases in developed countries, there has come the realization that genetic and epigenetic regulation in diseases are a major cause of disability, death, and human tragedy. Here, I discuss current knowledge about this matter including the diagnosis, counseling, treatment and management as well as some current therapeutic interventions such as gene, stem cell, epigenetic therapies and future directions in the field.

by Kerstin Grund  , Dominik Sturm  , Christian Sutter  , Felix Sahm  , Katrin Hinderhofer  , Christian Kratz  , Daniel Schrimpf  , Andreas von Deimling  , Kristian W. Pajtler  , David TW Jones  , Stefan M. Pfister  and Nicola Dikow

Received: 01 September 2017;  Published: 05 December 2017;  doi: 10.21926/obm.genet.1704011

The MNP 2.0 study offers a specified oncologic diagnosis and the detection of possible therapeutic targets for a large cohort of pediatric neurooncologic patients. With the parents / patients agreement the study also performs germline analysis of all included patients and thereby translates scientific analysis in medical genetic care. This requires a workflow in consideration of the conditions of a multicenter study and the legal stipulations, as well as a closed interdisciplinary cooperation. We present our elabor [...]

by Myrto Poulou  and Maria Tzetis

Received: 31 July 2017;  Published: 01 November 2017;  doi: 10.21926/obm.genet.1704010

Cystic Fibrosis (CF) is one of the commonest autosomal recessive genetic diseases that show a high carrier frequency amongst Caucasian populations. Although there has been tremendous progress in the available therapies, compared to the past, the disease is still associated with significant morbidity and mortality. Because of the severe clinical manifestations and the shortened life expectancy of patients, population based carrier screening, to identify heterozygous carrier couples at risk of having affected childre [...]