Clinical findings and a DNA methylation signature in kindreds with alterations in ZNF711.

ZNF711 is one of eleven zinc-finger genes on the X chromosome that have been associated with X-linked intellectual disability. This association is confirmed by the clinical findings in 20 new cases in addition to 11 cases previously reported. No consistent growth aberrations, craniofacial dysmorphology, malformations or neurologic findings are associated with alterations in ZNF711. The intellectual disability is typically mild and coexisting autism occurs in half of the cases. Carrier females show no manifestations. A ZNF711-specific methylation signature has been identified which can assist in identifying new cases and in confirming the pathogenicity of variants in the gene.

Racialized algorithms for kidney function: Erasing social experience.

The rise of evidence-based medicine, medical informatics, and genomics --- together with growing enthusiasm for machine learning and other types of algorithms to standardize medical decision-making --- has lent increasing credibility to biomedical knowledge as a guide to the practice of medicine. At the same time, concern over the lack of attention to the underlying assumptions and unintended health consequences of such practices, particularly the widespread use of race-based algorithms, from the simple to the complex, has caught the attention of both physicians and social scientists. Epistemological debates over the meaning of "the social" and "the scientific" are consequential in discussions of race and racism in medicine. In this paper, we examine the socio-scientific processes by which one algorithm that "corrects" for kidney function in African Americans became central to knowledge production about chronic kidney disease (CKD). Correction factors are now used extensively and routinely in clinical laboratories and medical practices throughout the US. Drawing on close textual analysis of the biomedical literature, we use the theoretical frameworks of science and technology studies to critically analyze the initial development of the race-based algorithm, its uptake, and its normalization. We argue that race correction of kidney function is a racialized biomedical practice that contributes to the consolidation of a long-established hierarchy of difference in medicine. Consequentially, correcting for race in the assessment of kidney function masks the complexity of the lived experience of societal neglect that damages health.

Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development.

A copy-number variant (CNV) of 16p11.2 encompassing 30 genes is associated with developmental and psychiatric disorders, head size, and body mass. The genetic mechanisms that underlie these associations are not understood. To determine the influence of 16p11.2 genes on development, we investigated the effects of CNV on craniofacial structure in humans and model organisms. We show that deletion and duplication of 16p11.2 have "mirror" effects on specific craniofacial features that are conserved between human and rodent models of the CNV. By testing dosage effects of individual genes on the shape of the mandible in zebrafish, we identify seven genes with significant effects individually and find evidence for others when genes were tested in combination. The craniofacial phenotypes of 16p11.2 CNVs represent a model for studying the effects of genes on development, and our results suggest that the associated facial gestalts are attributable to the combined effects of multiple genes.

Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is a defining ciliopathy, notable for extensive allelic and genetic heterogeneity, almost all of which has been identified through sequencing. Recent data have suggested that copy-number variants (CNVs) also contribute to BBS. We used a custom oligonucleotide array comparative genomic hybridization (aCGH) covering 20 genes that encode intraflagellar transport (IFT) components and 74 ciliopathy loci to screen 92 unrelated individuals with BBS, irrespective of their known mutational burden. We identified 17 individuals with exon-disruptive CNVs (18.5%), including 13 different deletions in eight BBS genes (BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, BBS7, BBS9, and NPHP1) and a deletion and a duplication in other ciliopathy-associated genes (ALMS1 and NPHP4, respectively). By contrast, we found a single heterozygous exon-disruptive event in a BBS-associated gene (BBS9) in 229 control subjects. Superimposing these data with resequencing revealed CNVs to (1) be sufficient to cause disease, (2) Mendelize heterozygous deleterious alleles, and (3) contribute oligogenic alleles by combining point mutations and exonic CNVs in multiple genes. Finally, we report a deletion and a splice site mutation in IFT74, inherited under a recessive paradigm, defining a candidate BBS locus. Our data suggest that CNVs contribute pathogenic alleles to a substantial fraction of BBS-affected individuals and highlight how either deletions or point mutations in discrete splice isoforms can induce hypomorphic mutations in genes otherwise intolerant to deleterious variation. Our data also suggest that CNV analyses and resequencing studies unbiased for previous mutational burden is necessary to delineate the complexity of disease architecture.

Consumer Information and Treatment Resources for Posttraumatic Stress Disorder: Within Reach but Not Grasp.

In the context of multiple treatment options for posttraumatic stress disorder (PTSD) and a large, growing need for consumer information regarding accessible and effective treatments, this article identifies and reviews available information and treatment resources. Multiple search strategies identified a suite of information sources, including meta-analyses and systematic reviews of PTSD treatments, the program evaluation and implementation literature, the economics literature, Internet sites, and other resources for veteran and civilian consumers. Resources were evaluated with regard to their target audiences, depth and breadth of treatment options covered, nature of the information provided, and accessibility to consumers. A large body of research covers the various treatments and sets of treatment guidelines for PTSD. Despite the extensive scientific information targeted at providers and researchers, the quality, accessibility, and usability of the published research varies widely. The Veterans Health Administration provides the most extensive information on various treatment options and where to obtain treatment within that system. Publicly available websites provide information on multiple treatment options, but information to help nonveterans navigate treatment choices is limited. Published reports of PTSD program-evaluation and implementation studies are sparse. Information on PTSD treatment options available to consumers can be overwhelming and confusing, which places an unnecessary burden on an already vulnerable group of patients and their families. Exacerbating the situation is the shortage of program-evaluation and implementation research. The dearth of centralized and accessible information related to nonveteran PTSD patient groups needs to be addressed.