Mutation of the diamond-blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes.

The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7(Mtu) and Rps7(Zma)) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes.

Functional outcomes of posterior vaginal wall repair and prespinous colpopexy with biological small intestinal submucosal (SIS) graft.

PURPOSE: Surgical management of posterior vaginal wall prolapse has variable functional outcomes. Synthetic and biological grafts are used to improve outcomes and reduce failures. The objective of this study was to determine the functional outcomes and its implications on patient-reported quality of life of a technique of posterior vaginal wall repair and prespinous colpopexy with biological small intestinal submucosal (SIS) graft in the management of posterior vaginal wall prolapse. METHODS: This prospective cohort study was conducted in a urogynaecology subspecialty center in the UK. Women with moderate degree rectocele or more, with or without other compartmental prolapse underwent posterior vaginal wall repair and prespinous colpopexy with SIS graft over a 3-year period. ICIQ vaginal symptoms questionnaires were used pre-operatively and at 6 months post-operatively to assess functional outcomes. The Wilcoxon signed R test was used to analyze the results. RESULTS: 50 women underwent posterior repair with SIS graft (27 with concomitant procedures). There was a statistically significant improvement (p < 0.0001) in the vaginal symptoms and sexual matters scores at 6-month follow-up in all the women. The quality of life scores also improved significantly (p < 0.0001) in all the women. Concomitant pelvic surgery did not affect the outcomes (p < 0.0001). There were no significant intra- or post-operative complications. CONCLUSION: Posterior vaginal wall repair and prespinous colpopexy with biological SIS graft is an effective surgical option for managing women with posterior vaginal wall prolapse with or without other concomitant compartmental defects.

Human herpes virus 8-positive germinotropic lymphoproliferative disorder: first case diagnosed in the UK, literature review and discussion of treatment options.

We present this case of human herpes virus 8-positive germinotropic lymphoproliferative disorder in a 20-year-old woman seen in the surgical oncology clinic for localised lymphadenopathy. This is the first case to be reported in the UK, and we discuss it along with a literature review including investigations and treatment options. This will demonstrate the importance of preoperative workup and multidisciplinary teamwork in deciding management plans and serve as a guide for future encounters of this rare condition in clinical practice.