Overview of Gene Special Issue “Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis”

In this Special Issue of Genes entitled “Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis”, evidence is presented which suggests that congenital, idiopathic scoliosis, and arthrogryposis share similar overlapping, but also distinct etiopathogenic mechanisms, including connective tissue and neuromuscular mechanisms [...

Marshfield Clinic Personalized Medicine Research Project (PMRP): design, methods and recruitment for a large population-based biobank

Objectives: The objective of this paper is to summarize the planning for Phase I of the Marshfield Clinic Personalized Medicine Research Project (PMRP) and to describe the recruitment efforts in the first 2 years. Methods: The purpose of Phase I of the PMRP was to develop a large population-based biobank with DNA, plasma and serum samples to facilitate genomics research. Planning and consultation was facilitated with three external boards: the Ethics and Security Advisory Board; the Scientific Advisory Board; and the Community Advisory Group. Commencing in September 2002, residents aged 18 and above who resided in 1 of 19 zip codes surrounding Marshfield, WI, USA, were invited to participate. After providing written informed consent, participants completed brief questionnaires that included questions about demographics, some environmental exposures, family history of disease, and adverse drug reactions, as well as family members living in the study area. Participants provided 50 ml of blood from which DNA was extracted and plasma and serum samples were stored. The informed consent document allowed access to electronic medical records and included language about non-disclosure of personal research results. A tick-off box was also included so that participants could either allow or decline subsequent recontact for future research studies. Results: A total of 17,463 subjects were enrolled during the first 23 months of recruitment (44.3% of the residents who the Research Project Assistants were able to contact). The participants ranged in age from 18 to 98.5 years (mean = 48.9, median = 48); 57.2% (n = 9986) were female. Self-reported race in the study cohort was similar to the year 2000 census for Wood County, WI, USA, with the majority (98%) reporting themselves to be White Caucasian. The majority of subjects (n = 13,391, 76.7%) indicated that they had German ancestry. Only 142 participants (< 1%) opted out on the consent form for contact for future studies. The majority of the cohort reported that their current area of residence was a suburb, city or village (n = 10630, 60.87%); the remainder reported residence in a rural home or hobby farm (n = 5365, 30.72%), or a working farm or ranch (n = 1451, 8.31%). More than half the cohort (n = 9409, 53.88%) had lived on a working farm at some point in their life. Conclusion: The PMRP database will allow research in three areas: genetic epidemiology, pharmacogenetics, and population genetics. The size and the stability of the population as well as the relative ethnic homogeneity will help facilitate longitudinal studies with valid research results that are not biased by population stratification

A male infant with Xq22.2q22.3 duplication containing PLP1 and MID2

Abstract Background The Xq22.2 q23 is a complex genomic region which includes the genes MID2 and PLP1 associated with FG syndrome 5 and Pelizaeus–Merzbacher disease, respectively. There is limited information regarding the clinical outcomes observed in patients with deletions within this region. Methods We report on a male infant with intrauterine growth retardation (IUGR) who developed head titubation and spasticity during his postnatal hospital course. Results Chromosome microarray revealed a 6.7 Mb interstitial duplication of Xq22.2q22.3. Fluorescence in situ hybridization showed that the patient's mother also possessed the identical duplication in the Xq22.3q22.3 region. Among the 34 OMIM genes in this interval, the duplication of the PLP1 (OMIM# 300401) and MID2 (OMIM# 300204) appears to be the most significant contributors to the patient's clinical features. Mutations and duplications of PLP1 are associated with X‐linked recessive Pelizaeus–Merzbacher disease (PMD). A single case of a Xq22.3 duplication including the MID2 has been reported in boy with features of FG syndrome. However, our patient's clinical features are not consistent with the FG syndrome phenotype. Conclusion Our patient's clinical features appear to be influenced by the PLP1 duplication but the clinical effect of other dosage sensitive genes influencing brain development cannot be ruled out

Amygdala activation to masked happy facial expressions

The amygdala has a key role in automatic non-conscious processing of emotions. Highly salient emotional stimuli elicit amygdala activity, and happy faces are among the most rapidly perceived facial expressions. In backward masking paradigms, an image is presented briefly and then masked by another stimulus. However, reports of amygdala responses to masked happy faces have been mixed. In the present study, we used functional magnetic resonance imaging (fMRI) to examine amygdala activation to masked happy, sad, and neutral facial expressions. Masked happy faces elicited greater amygdala activation bilaterally as compared to masked sad faces. Our findings indicate that the amygdala is highly responsive to non-consciously perceived happy facial expressions. (JINS, 2010, 16, 383–387.

Clinical Geneticists' Views of VACTERL/VATER Association

VACTERL association (sometimes termed “VATER association” depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co-occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory-based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association