Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.

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Central neurocytoma (CN) is described as a rare intra-ventricular benign neuronal tumor of the brain. Two primary tumors first diagnosed as malignant and extra-ventricular neurocytomas are reported here. Histologically, the tumor of the first patient, a forty-one-year-old man, consisted of monotonous cells with round nuclei, but no fibrillar background. The second tumor, in a nineteen-year-old girl, showed areas of moderately pleomorphic round cells, with numerous rosettes and ganglion cell differentiation, in an abundant fibrillary network. Both presented calcifications. Mitoses were more frequent in recurrences and spinal locations than in the primaries. All tumors stained strongly for synaptophysin, and GFAP was partly positive in the first case only. Patients received post-surgical radiotherapy and were still alive eight and six years, respectively, after initial surgery. The interpretation of atypical cases, such as ours is not easy: the diagnoses finally retained were oligodendroglioma in the first case and ganglioneuroblastoma in the second case. Furthermore, neurocytomas atypical either by their unusual topographical or histological presentation or by their poor prognosis, have been frequently entitled in this way on synaptophysin positivity. So, we were prompted to reassess the entity of CN, seventeen years after the first description, to re-appreciate the reality of anatomo-clinical variants and to discuss the value of synaptophysin positivity in these tumors. In conclusion, it seems preferable to individualize true classical CN, which has a favorable outcome, from so-called extra-ventricular, atypical and anaplastic, clinically malignant neurocytomas for which complementary treatment is required.

2048 Background: The outcome of patients with high-grade gliomas remains poor despite modern therapeutic arsenal. The objective of this study was to assess the feasibility and efficacy of radiotherapy (RT) given immediately after hyperbaric oxygenation (HBO) with Stupp protocol. Methods: All patients with histologically confirmed high-grade gliomas from 2008 till 2011 coveraged at GHSR hospital were enrolled. Patients underwent Stupp protocol consisting in 60 Gy RT with a daily dose of 2 Gy for 5 days per week administrated immediately after HBO. Temozolomide (TMZ) was administrated at the daily dose 75 mg/m², 7 days per week followed by 6 cycles of TMZ 150 to 200 mg/m² for 5 days each 28 day-cycle. HBO schedule was approximately 15 min of compression with air, 60 min of 100% oxygen inhalation and 10 min of decompression with oxygen. Results: A total of 21 patients were diagnosed and histologically confirmed high grade gliomas. Five were excluded because of HBO contraindications. Twelve patients (75%) had undergone debulking surgery. The time interval from completion of decompression to start of irradiation was less than 15 minutes (mean 14.25, range 8-18). Twelve patients (75%) received the complete dose of RT and TMZ. HBO was completed for 7 (43.75%). Five (31.25%) were temporarily stopped and 4 (25%) were definitively stopped. One patient (6.25%) suffered from pancytopenia with grade 4 thrombopenia and grade 3 neutropenia. The median follow up was 46.95 weeks (range 5.7-108.3). Nine patients (56.25%) are still alive. Four (25%) have a survival more than 16 months. Conclusions: HBO with Stupp protocol is feasible and promising but requiring a large multicentric study.

Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. Whole exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A), as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss of function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.