Journal of medical genetics
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Chromosome 22q loss of heterozygosity (LOH) is the most common allelic loss in benign meningioma and is thought to be the earliest initiating event in meningioma formation. We used published data and logistic regression to evaluate the association of 22q LOH with age at diagnosis in 318 transitional, fibroblastic, and meningothelial meningiomas. After adjustment for anatomical location, the odds ratio of 22q LOH per year of age was >1 in each histological type of meningioma, and was significantly >1 in transitional and fibroblastic meningioma. This finding is compatible with involvement of the neurofibromatosis 2 tumour suppressor gene, NF2, on chromosome 22q in the high incidence of benign meningioma in the elderly.
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Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two conditions which were previously believed to be completely separate entities. BM is a relatively mild dominantly inherited disorder characterised by proximal weakness and distal joint contractures. UCMD was originally described as an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. Here we review the clinical phenotypes of BM and UCMD and their diagnosis and management, and provide an overview of the current knowledge of the pathogenesis of collagen VI related disorders.
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Comparative Study
Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.
A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on kappa-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant mu-opioid receptor. ⋯ Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics.
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Sepsis, organ failure, and shock remain common among patients with moderate to severe burn injuries. The inability of clinical factors to identify at-risk patients suggests that genetic variation may influence the risk for serious infection and the outcome from severe injury. ⋯ The TLR4 +896 and TNF-alpha -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.