RESUMO
We identified an MSH6 mutation (c.10C>T, p.Gln4*) causing Lynch syndrome (LS) in 11 French Canadian (FC) families from the Canadian province of Quebec. We aimed to investigate the molecular and clinical implications of this mutation among FC carriers and to assess its putative founder origin. We studied 11 probands and 27 family members. Additionally 6433 newborns, 187 colorectal cancer (CRC) cases, 381 endometrial cancer (EC) cases and 179 additional controls, all of them from Quebec, were used. Found in approximately 1 of 400 newborns, the mutation is one of the most common LS mutations described. We have found that this mutation confers a greater risk for EC than for CRC, both in the 11 studied families and in the unselected cases: EC [odds ratio (OR) = 7.5, p < 0.0001] and CRC (OR = 2.2, p = 0.46). Haplotype analyses showed that the mutation arose in a common ancestor, probably around 430-656 years ago, coinciding with the arrival of the first French settlers. Application of the results of this study could significantly improve the molecular testing and clinical management of LS families in Quebec.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA/genética , Etnicidade/genética , Efeito Fundador , Mutação , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Criança , Pré-Escolar , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/genética , Família , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Heterozigoto , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Quebeque , Risco , Adulto JovemRESUMO
The tonic stretch reflex threshold in children with cerebral palsy (CP) was measured to determine its test-retest reliability and its concurrent validity as a potential measure of spasticity. Fourteen children with spastic CP aged 6 to 18 years were tested on three separate occasions for clinical spasticity and stretch reflex thresholds of affected elbow flexors. Electromyographic (EMG) recordings were obtained by surface electrodes for elbow flexors and extensors during mechanical displacements of the passive joint towards extension. Displacements were produced by a torque motor at seven velocities which randomly varied from trial to trial. EMG activity was measured in the stretched flexor muscles to determine threshold angles and velocities for each velocity of stretch. These were plotted on a velocity-angle-phase diagram and regression analysis was used to determine the static stretch reflex threshold for each participant. The measure showed good test-retest reliability for the group (ICC 0.73, p<0.001) whereas a significant correlation between the measure and the clinical spasticity scale was not found. This technique is a potential outcome variable for measuring the efficacy of treatments aimed at decreasing spasticity in children with CP.
