Genetic basis of human disorders of gonadal development

South Africa is unique in the arena of Intersex, in that for unknown reasons we have a very high percentage of ovotesticular DSD (True Hermaphrodite). Whereas ovotesticular DSD is the least common cause of hermaphroditism in other parts of the world, it is the most common cause of hermaphroditism in South Africa. There have been several studies in the past to determine the cause of ovotesticular DSD in our population but none of these studies found appropriate answers. The current state of understanding implicates signaling and signal transduction molecules and transcription factors suggesting that it is likely not all of the genetic factors involved have already been identified. It was hypothesized that exome sequencing of individuals with DGDs will identify new mutations and genes for these conditions. Therefore, this study aims to identify additional genes that are associated with ovotesticular DSD. By using a whole-genome sequencing approach we expected to be able to identify rare variants with this condition and determine the prevalence of mutations in these genes in the ovotesticular DSD population. After obtaining informed consent, blood specimen was obtained from eleven out of fifteen patients who had histological diagnosis of Ovotesticular DSD at the Red Cross War Memorial Hospital over a 10 year period. Blood specimen was also obtained from the biological parents of these children and sent to the Ostrer laboratory for whole genome sequencing and analysis. At the Ostrer laboratory, high quality DNA was extracted from blood for all of subjects and lymphoblastoid cell lines were created. Following sample preparation using the Illumina library preparation kit, sequencing was accomplished using paired-end sequencing technology on an Illumina HiSeq2000 sequencer. The data from the Illumina sequencers was analyzed first using the Illumina sequencing data analysis pipeline for quality control. Paired end reads were aligned to the Human Reference Genome (NCBI Build 36) using the BWA software. Each alignment was assigned a mapping quality score by BWA, which is the Phredscaled probability that a read is misaligned. The basic functional annotation of SNPs/Indels is performed by ANNOVAR. The clinical features of these patients was consistent with those found by other studies on Ovotesticular DSD in South Africa and it also showed the same pattern of variation to the clinical features of Ovotesticular DSD from other parts of the world. Similar to previous South African studies, this study found no convincing gene mutations as the possible etiology of Ovotesticular DSD in South Africa. Whiles gene mutations such as duplication of SOX 9 have been found in patients with XX Ovotesticular DSD from outside South Africa, this study could not identify any such mutations. This further adds to the suspicion that the unique features of Ovotesticular DSD in South Africa suggests a different etiology from that of other parts of the world. In conclusion, the etiology of Ovotesticular DSD in South Africa still remains elusive. It is however possible that a genetic mutation may be found from a more critical analysis of the genome of the patients and their parents

Retrocaval Ureter: Report of Two Cases

Retrocaval ureter (RCU) is a rare congenital anomaly in which the ureter passes posterior to the inferior vena cava (IVC). A little over 200 cases have been reported worldwide since Hochstetter’s first report in 1893. We present two cases of retrocaval ureter which were successfully managed at the Cape Coast Teaching Hospital in Ghana. Case 1. A 55-year-old woman presented with a history of dull right flank pain of 2 years duration. Physical examination and basic laboratory investigations performed on her were normal. Abdominal ultrasound showed right hydronephrosis and a retrograde right ureteropyelogram (RPG) showed right hydroureteronephrosis with an “S” shaped proximal ureter. A diagnosis of retrocaval ureter was made and confirmed at surgery. Case 2. A 25-year-old man presented with dull intermittent right flank pain of 1 year duration. Clinical examination and laboratory investigation were normal. Abdominal ultrasound showed right hydronephrosis and a CT urogram made a diagnosis of retrocaval ureter which was confirmed at surgery. Conclusion. Retrocaval ureter is a rare congenital anomaly that is now increasingly being reported. Surgical treatment of symptomatic cases successfully relieves symptoms

Dorsal Onlay Oral Mucosa Graft Urethroplasty: A Case Report and Review of Literature

The use of buccal mucosa grafts in urethral reconstruction for complex anterior urethral strictures has gained popularity over the years with very good outcomes reported in literature. We report on the successful repair of a complex anterior urethral stricture in a 14-year-old boy following catheterization using this method at the Komfo Anokye Teaching Hospital. The aim is to describe the method of dorsal onlay oral mucosa graft urethroplasty and to review the literature

Adaptation of the Wound Healing Questionnaire universal-reporter outcome measure for use in global surgery trials (TALON-1 study): mixed-methods study and Rasch analysis

BackgroundThe Bluebelle Wound Healing Questionnaire (WHQ) is a universal-reporter outcome measure developed in the UK for remote detection of surgical-site infection after abdominal surgery. This study aimed to explore cross-cultural equivalence, acceptability, and content validity of the WHQ for use across low- and middle-income countries, and to make recommendations for its adaptation.MethodsThis was a mixed-methods study within a trial (SWAT) embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partners (TALON-1). Structured interviews and focus groups were used to gather data regarding cross-cultural, cross-contextual equivalence of the individual items and scale, and conduct a translatability assessment. Translation was completed into five languages in accordance with Mapi recommendations. Next, data from a prospective cohort (SWAT) were interpreted using Rasch analysis to explore scaling and measurement properties of the WHQ. Finally, qualitative and quantitative data were triangulated using a modified, exploratory, instrumental design model.ResultsIn the qualitative phase, 10 structured interviews and six focus groups took place with a total of 47 investigators across six countries. Themes related to comprehension, response mapping, retrieval, and judgement were identified with rich cross-cultural insights. In the quantitative phase, an exploratory Rasch model was fitted to data from 537 patients (369 excluding extremes). Owing to the number of extreme (floor) values, the overall level of power was low. The single WHQ scale satisfied tests of unidimensionality, indicating validity of the ordinal total WHQ score. There was significant overall model misfit of five items (5, 9, 14, 15, 16) and local dependency in 11 item pairs. The person separation index was estimated as 0.48 suggesting weak discrimination between classes, whereas Cronbach's α was high at 0.86. Triangulation of qualitative data with the Rasch analysis supported recommendations for cross-cultural adaptation of the WHQ items 1 (redness), 3 (clear fluid), 7 (deep wound opening), 10 (pain), 11 (fever), 15 (antibiotics), 16 (debridement), 18 (drainage), and 19 (reoperation). Changes to three item response categories (1, not at all; 2, a little; 3, a lot) were adopted for symptom items 1 to 10, and two categories (0, no; 1, yes) for item 11 (fever).ConclusionThis study made recommendations for cross-cultural adaptation of the WHQ for use in global surgical research and practice, using co-produced mixed-methods data from three continents. Translations are now available for implementation into remote wound assessment pathways