Heterozygous loss-of-function variants significantly expand the phenotypes associated with loss of GDF11.

PURPOSE: Growth differentiation factor 11 (GDF11) is a key signaling protein required for proper development of many organ systems. Only one prior study has associated an inherited GDF11 variant with a dominant human disease in a family with variable craniofacial and vertebral abnormalities. Here, we expand the phenotypic spectrum associated with GDF11 variants and document the nature of the variants. METHODS: We present a cohort of six probands with de novo and inherited nonsense/frameshift (4/6 patients) and missense (2/6) variants in GDF11. We generated gdf11 mutant zebrafish to model loss of gdf11 phenotypes and used an overexpression screen in Drosophila to test variant functionality. RESULTS: Patients with variants in GDF11 presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). gdf11 mutant zebrafish show craniofacial abnormalities and body segmentation defects that match some patient phenotypes. Expression of the patients' variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants in our cohort are partial LOF variants. CONCLUSION: GDF11 is needed for human development, particularly neuronal development, and LOF GDF11 alleles can affect the development of numerous organs and tissues.

Relational frame theory: an overview of the controversy.

Although Skinner's Verbal Behavior (1957) was published over 50 years ago, behavior-analytic research on human language and cognition has been slow to develop. In recent years, a new behavioral approach to language known as relational frame theory (RFT) has generated considerable attention, research, and debate. The controversy surrounding RFT can be difficult to fully appreciate, partly because of the complexity of the theory itself and partly because the debate has spanned several years and several journals. The current paper aims to provide a concise overview of RFT and a summary of key points of debate and controversy.

Using video technology to disseminate behavioral procedures: a review of Functional Analysis: a Guide for Understanding Challenging Behavior (DVD).

Although applied behavior analysis has generated many highly effective behavior-change procedures, the procedures have not always been effectively disseminated. One solution to this problem is the use of video technology, which has been facilitated by the ready availability of video production equipment and software and multiple distribution methods (e.g., DVD, online streaming). We review a recent DVD that was produced to disseminate the successful experimental functional analysis procedure. The review is followed by general recommendations for disseminating behavior-analytic procedures via video technology.