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The alcohol dehydrogenase (ADH) family has evolved into at least eight ADH classes during vertebrate evolution. We have characterized three prevertebrate forms of the parent enzyme of this family, including one from an urochordate (Ciona intestinalis) and two from cephalochordates (Branchiostoma floridae and Branchiostoma lanceolatum). An evolutionary analysis of the family was performed gathering data from protein and gene structures, exon-intron distribution, and functional features through chordate lines. ⋯ Phylogenetic analysis and chromosomal mapping of the vertebrate Adh gene cluster suggest that family expansion took place by tandem duplications, probably concurrent with the extensive isoform burst observed before the fish/tetrapode split, rather than through the large-scale genome duplications also postulated in early vertebrate evolution. The absence of multifunctionality in lower chordate ADHs and the structures compared argue in favor of the acquisition of new functions in vertebrate ADH classes. Finally, comparison between B. floridae and B. lanceolatum Adhs provides the first estimate for a cephalochordate speciation, 190 million years ago, probably concomitant with the beginning of the drifting of major land masses from the Pangea.
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Congenital myasthenic syndromes comprise heterogeneous genetic diseases characterized by compromised neuromuscular transmission. Congenital myasthenic syndromes are classified as presynaptic, synaptic, or postsynaptic, depending on the primary defect's location within the neuromuscular junction. Presynaptic forms are the rarest, affecting an estimated 7-8% of patients; synaptic forms account for approximately 14-15% of patients; and the remaining 75-80% are attributable to postsynaptic defects. ⋯ The identification of congenital myasthenic syndromes subtypes will prove important in the treatment of these patients. Different drugs may be beneficial, or should be avoided because they are ineffective or worsen some forms of congenital myasthenic syndromes. We explore the classification, clinical manifestations, electrophysiologic features, genetics, and treatment responses of each congenital myasthenic syndrome subtype.
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Curr Opin Rheumatol · Jan 2006
ReviewFamilial Mediterranean fever and the other autoinflammatory syndromes: evaluation of the patient with recurrent fever.
The aim of this article is to summarize recent clinical, genetic and pathophysiologic findings of familial Mediterranean fever and several of the other systemic autoinflammatory diseases, a recently recognized group of disorders characterized by seemingly unprovoked inflammation but lacking high-titer autoantibodies. Genetic and clinical tools are improving the ability of the clinician to better approach patients with periodic fever and inflammation. ⋯ The identification of the genes and proteins mutated in many of the autoinflammatory diseases has broadened our understanding of the regulation of inflammation and the immune system, and provided the basis for the use of targeted therapies in these syndromes. We propose an algorithm for the evaluation of a patient with periodic fever, taking into account the patient's age, ethnicity, symptoms and signs, and results from laboratory and genetic testing.