Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data.

Background: Human genome sequencing has transformed our understanding of genomic variation and its relevance to health and disease, and is now starting to enter clinical practice for the diagnosis of rare diseases. The question of whether and how some categories of genomic findings should be shared with individual research participants is currently a topic of international debate, and development of robust analytical workflows to identify and communicate clinically relevant variants is paramount.

Methods: The Deciphering Developmental Disorders (DDD) study has developed a UK-wide patient recruitment network involving over 180 clinicians across all 24 regional genetics services, and has performed genome-wide microarray and whole exome sequencing on children with undiagnosed developmental disorders and their parents.

Benign peripheral nerve tumors: treatment algorithm and reconstructive options.

Peripheral nerve tumors are mostly benign; however, their excision can result in profound deficits. Nerve reconstruction strategies offer techniques to minimize morbidity. In this prospective study, 20 consecutive patients with benign peripheral nerve tumors were treated using a single-stage surgical paradigm between 2003 and 2007.

Inhibition of protein-tyrosine phosphatases by mild oxidative stresses is dependent on S-nitrosylation.

Previous studies have shown that a Ca(2+)-dependent nitric-oxide synthase (NOS) is activated as part of a cellular response to low doses of ionizing radiation. Genetic and pharmacological inhibitor studies linked this NO signaling to the radiation-induced activation of ERK1/2. Herein, a mechanism for the radiation-induced activation of Tyr phosphorylation-dependent pathways (e.