RESUMO
X-linked forms of retinitis pigmentosa (XLRP) are among the most severe because of their early onset, often leading to significant visual impairment before the fourth decade. RP3, genetically localized at Xp21.1, accounts for 70% of XLRP in different populations. The RPGR (Retinitis Pigmentosa GTPase Regulator) gene that was isolated from the RP3 region is mutated in 20% of North American families with XLRP. From mutation analysis of 27 independent XLRP families, we have identified five novel RPGR mutations in 5 of the families (160delA, 789 A>T, IVS8+1 G>C, 1147insT and 1366 G>A). One of these mutations was detected in a family from Chile. Hum Mutat 17:151, 2001.
Assuntos
Proteínas de Transporte/genética , Proteínas do Olho , Retinose Pigmentar/genética , Cromossomo X/genética , DNA/química , DNA/genética , Análise Mutacional de DNA , Feminino , Mutação da Fase de Leitura , Ligação Genética , Humanos , Masculino , Mutagênese Insercional , Mutação , Mutação de Sentido Incorreto , Retinose Pigmentar/patologia , Deleção de SequênciaRESUMO
X-linked forms of retinitis pigmentosa (XLRP) are among the most severe, because of their early onset, often leading to significant vision loss before the 4th decade. Previously, the RP15 locus was assigned to Xp22, by linkage analysis of a single pedigree with "X-linked dominant cone-rod degeneration." After clinical reevaluation of a female in this pedigree identified her as affected, we remapped the disease to a 19.5-cM interval (DXS1219-DXS993) at Xp11.4-p21.1. This new interval overlapped both RP3 (RPGR) and COD1. Sequencing of the previously published exons of RPGR revealed no mutations, but a de novo insertion was detected in the new RPGR exon, ORF15. The identification of an RPGR mutation in a family with a severe form of cone and rod degeneration suggests that RPGR mutations may encompass a broader phenotypic spectrum than has previously been recognized in "typical" retinitis pigmentosa.
Assuntos
Éxons/genética , Ligação Genética/genética , Mutação/genética , Fases de Leitura Aberta/genética , Retinose Pigmentar/genética , Cromossomo X/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Feminino , Haplótipos/genética , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Recombinação Genética/genéticaAssuntos
Proteínas do Olho , Proteínas/genética , Retinose Pigmentar/genética , Cromossomo X , Sequência de Aminoácidos , Sequência de Bases , Efeito Fundador , Mutação da Fase de Leitura , Proteínas de Ligação ao GTP , Deleção de Genes , Ligação Genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana , Dados de Sequência Molecular , Terra Nova e Labrador , Mutação Puntual , Análise de Sequência de DNA , Cromossomo X/genéticaRESUMO
Previous studies on cycling cadence have focused on the economy of the cadence, in search of the optimal pedal cadence. The purpose of this study was to determine the hemodynamic changes associated with varying pedal cadence at a constant workload. It was hypothesized that increased pedal cadence would enhance the skeletal muscle pump, resulting in elevation of cardiac output. Seven cyclists were enlisted to cycle at 200 watts at pedal cadences of 70, 90 and 110 rpm (random order). Oxygen uptake, heart rate, stroke volume, cardiac output, blood pressure, and vascular resistance were determined. As has been previously shown, oxygen uptake increased with increased cadence (70, 90, 110 rpm) at this workload. Heart rate, stroke volume, cardiac output and blood pressure were increased, and vascular resistance decreased, with increased cadence. Cardiac output increased (34%) in excess of the increase in oxygen uptake (15%) as shown by the decrease (-14.5%) in the arterial-venous oxygen difference occurring with increasing cadence. Apparently, even though the workload was constant, the increase in pedal cadence resulted in a more effective skeletal-muscle pump which increased muscle blood flow and venous return. It is not known if this might contribute to the natural selection of higher cadences by cycling athletes, even though there is reduced economy.
