No abstract

Molecular characterization of chromosomal rearrangements is a powerful resource in identification of genes associated with monogenic disorders. We describe the molecular characterization of a balanced familial chromosomal translocation, t(16;22)(p13.3;q11.2), segregating with congenital lamellar cataract. This led to the discovery of a cluster of lens-derived expressed sequence tags (ESTs) close to the 16p13.3 breakpoint. This region harbors a locus associated with cataract and microphthalmia. Long-range PCR and 16p13.3 breakpoint sequencing identified genomic sequence in a human genome sequence gap, and allowed identification of a novel four-exon gene, designated TMEM114, which encodes a predicted protein of 223 amino acids. The breakpoint lies in the promoter region of TMEM114 and separates the gene from predicted eye-specific upstream transcription factor binding sites. There is sequence conservation among orthologs down to zebrafish. The protein is predicted to contain four transmembrane domains with homology to the lens intrinsic membrane protein, LIM2 (also known as MP20), in the PMP-22/EMP/MP20 family. TMEM114 mutation screening in 130 congenital cataract patients revealed missense mutations leading to the exchange of highly-conserved amino acids in the first extracellular domain of the protein (p.I35T, p.F106L) in two separate patients and their reportedly healthy sibling and mother, respectively. In the lens, Tmem114 shows expression in the lens epithelial cells extending into the transitional zone where early fiber differentiation occurs. Our findings implicate dysregulation of expression of this novel human gene, TMEM114, in mammalian cataract formation.

In the era of "culture wars," instances where client and practitioner discuss political issues in therapy may become more frequent. This paper introduces the way in which "culture wars" manifest in today's societies and highlights the importance of therapeutic practitioners to engage with and explore their own views in relation to these polarising political debates. In doing so, this paper reflects upon the existing research focussing on the way in which "culture wars" enter the therapeutic encounter and highlights the feelings of anxiety and conflict that arise when practitioners are tasked with "talking politics" with clients. It considers the implications for practice and policy and concludes with recommendations for future scholarship, arguing for more culturally specific studies that examine how "culture wars" issues impact therapeutic work in a variety of international settings.