Lipomyelomeningocele is a form of spina bifida occulta with a distinct pathogenesis that differentiates it from open neural tube defects. Familial forms are rare and the condition may be polygenic. We report on 2 affected siblings with similar lesions and raise the possibility of an autosomal recessive pattern of inheritance with implications for genetic counselling.
Background:A case series of 20 consecutive patients followed for a minimum of 54 months following craniofacial resection of anterior skull base tumours is presented, with the aim of identifying complications and factors influencing survival. Methods: A retrospective review of a case series of 20 consecutive patients was carried out. Results: Dural invasion was significantly correlated with poorer survival. There was also a tendency for tumour grade and positive resection margins to be associated with poorer outcome. Most local recurrences occurred within 6 months of surgery, with the exception of adenocarcinoma of the ethmoids, in which recurrence occurred up to 36 months postoperatively. A variety of complications were encountered, with a marked decrease in serious complications from midway through the series.
Conclusions:The change in pattern of complications may be indicative of a learning curve, or the discontinuation of the use of lumbar drainage.
Racial differences in the incidence and rate of rupture of intracranial aneurysms are well recognized. A retrospective study of racial differences between Maori and European New Zealanders presenting to the Auckland Regional Neurosurgical Unit between 1985 and 1990 was conducted. It was found that the incidence per 100,000 of the population for all aneurysms was 14.3 for Europeans and 25.7 for Maoris. The mean age at rupture was 10 years earlier in Maoris with single aneurysms. A strong association between aneurysmal subarachnoid haemorrhage and cigarette smoking was found in both groups not only for single, but also for multiple aneurysms. Maoris were also found to have an abnormally high incidence of middle cerebral artery aneurysms and a low incidence of vertebrobasilar ones compared with Europeans.
Previous whole-exome sequencing has demonstrated that melanoma tumors harbor mutations in the GRIN2A gene. GRIN2A encodes the regulatory GluN2A subunit of the glutamate-gated N-methyl-d-aspartate receptor (NMDAR), involvement of which in melanoma remains undefined. Here, we sequenced coding exons of GRIN2A in 19 low-passage melanoma cell lines derived from patients with metastatic melanoma. Potential mutation impact was evaluated in silico, including within the GluN2A crystal structure, and clinical correlations were sought. We found that of 19 metastatic melanoma tumors, four (21%) carried five missense mutations in the evolutionarily conserved domains of GRIN2A; two were previously reported. Melanoma cells that carried these mutations were treatment-naïve. Sorting intolerant from tolerant analysis predicted that S349F, G762E, and P1132L would disrupt protein function. When modeled into the crystal structure of GluN2A, G762E was seen to potentially alter GluN1–GluN2A interactions and ligand binding, implying disruption to NMDAR functionality. Patients whose tumors carried non-synonymous GRIN2A mutations had faster disease progression and shorter overall survival (P < 0.05). This was in contrast to the BRAF V600E mutation, found in 58% of tumors but showing no correlation with clinical outcome (P = 0.963). Although numbers of patients in this study are small, and firm conclusions about the association between GRIN2A mutations and poor clinical outcome cannot be drawn, our results highlight the high prevalence of GRIN2A mutations in metastatic melanoma and suggest for the first time that mutated NMDARs impact melanoma progression.
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