Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome.

Adams-Oliver syndrome (AOS) is a rare, autosomal-dominant or -recessive disorder characterized primarily by aplasia cutis congenita and terminal transverse limb defects. Recently, we demonstrated that homozygous mutations in DOCK6 cause an autosomal-recessive form of AOS. In this study, we sought to determine the contribution of DOCK6 mutations to the etiology of AOS in several consanguineous families. In two of the five families studied, we identified two homozygous truncating mutations (a splice-site mutation and a frameshift duplication). DOCK6 sequencing revealed no mutation in the remaining three families, consistent with their autozygosity mapping and linkage-analysis results, which revealed a single candidate locus in 3p14.1 on three different haplotype backgrounds in the three families. Indeed, exome sequencing in one family revealed one missense mutation in EOGT (C3orf64), and subsequent targeted sequencing of this gene revealed a homozygous missense mutation and a homozygous frameshift deletion mutation in the other two families. EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine (O-GlcNAc) transferase, which is involved in the O-GlcNAcylation (attachment of O-GlcNAc to serine and threonine residues) of a subset of extracellular EGF-domain-containing proteins. It has a documented role in epithelial-cell-matrix interactions in Drosophila, in which deficiency of its ortholog causes wing blistering. Our findings highlight a developmental role of O-GlcNAcylation in humans and expand the genetic heterogeneity of autosomal-recessive AOS.

Perspectives of relatives and health care workers on care of terminally ill patients in the UK.

Two parallel questionnaires were used to explore perceptions of healthcare workers (HCWs) and the relatives of terminally ill patients on the quality of care received by the patients. There was general agreement between the two groups of respondents in most of the assessed areas. The relatives, however were more satisfied with the control of pain and psychological symptoms than the HCWs, and the HCWs perceived the control of diarrhea, skin problems, and swallowing problems more positively than did the relatives. There also was some variation between the two groups in their perception of the care received by the relatives during visits at the hospital, with the relatives' group being more positive. Although HCWs reported that time to deal with patients and their families was inadequate, the relatives' group was generally satisfied with the standards in place.