RESUMO
BACKGROUND: Usher syndrome (USH) is heterogeneous in nature and requires genetic test for diagnosis and management. Mutations in USH associated genes are reported in some populations except Russians. Here, we first time represented the mutation spectrum of a Russian USH cohort. METHODS: Twenty-eight patients with USH were selected from 3214 patients from Deaf-Blind Support Foundation "Con-nection" during 2014-2016 following the observational study NCT03319524. Complete ophthalmologic, ENT, and vestibular medical tests were done for clinical characterization. NGS, MLPA, and Sanger sequencing were considered for genetic analysis. RESULTS: Around 53.57% and 39.28% patients had USH1 and USH2, respectively; 17.85% cases (n = 5/28) had no known mutation. Eleven (73.33%) subjects showed variations in USH1 associated genes MYO7A (72.72%), CDH23 (9.09%), PCDH15 (9.09%), and USH1C (9.09%). Eleven mutations are detected in MYO7A where 54.54% are novel. MYO7A: p.Q18* was most frequent (27.27%) mutation and is associated with early manifestation and most severe clinical picture. Two novel mutations (p.E1301* and c.158-?_318+?del) are detected in PCDH15 gene. Around 90.90% patients suspected to be USH2 are confirmed by genetic testing. Eleven mutations detected in the USH2A gene, where 27.27% were novel. Most common USH2A mutation is p.W3955* (50%) followed by p.E767fs, p.R1653*, and c.8682-9A> G (20% each). CONCLUSION: The Russian USH cohort shows both novel and known USH mutations. Clinically the prevalence of USH2 is low (39.28%) and the frequency of MYO7A mutations responsible for USH1B is very high (63.63%, N = 7/11) compared to other cohorts. These seven patients carrying MYO7A mutations are preliminarily eligible for the UshStat® gene therapy.
Assuntos
Testes Genéticos , Terapia Genética , Miosinas/genética , Seleção de Pacientes , Síndromes de Usher/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Audiometria , Proteínas Relacionadas a Caderinas , Caderinas/genética , Proteínas de Ciclo Celular , Proteínas do Citoesqueleto , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Miosina VIIa , Oftalmoscopia , Federação Russa/epidemiologia , Tomografia de Coerência Óptica , Síndromes de Usher/epidemiologia , Síndromes de Usher/terapia , Testes de Função VestibularRESUMO
OBJECTIVE: To determine left ventricular isovolumic relaxation time (LV IRT) in normally developing and growth restricted fetuses (FGR) as an indicator of fetal cardiac afterload and neonatal systolic blood pressure. STUDY DESIGN: A prospective longitudinal study in 124 normally developing and 47 growth restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery pulsatility index (PI) were determined at 2-3 week intervals starting at 22-26 weeks of gestation until delivery. Renin and angiotensin I levels were measured by radioimmunoassay in umbilical venous blood after delivery. Systolic blood pressure was measured at day 1 and day 5 of postnatal life. To evaluate the association between LV IRT, gestational age and FHR, bivariate regression analyses were performed. RESULTS: Mean LV IRT (62+/-8 ms) was 29 percent longer in FGR as compared to the normal subset (47+/-6 ms) at all gestational ages (p<0.001). Mean postnatal active plasma renin level (7.78+/-S.D. 1.03 ng/ml) and postnatal angiotensin I level (4.21+/-0.70 ng/ml) in the FGR subset were significantly higher (p<0.001) than in the normal subset (4.81+/-1.04 ng/ml, renin and 2.69+/-0.44 ng/ml, angiotensin I). There was a significant difference (p<0.01) in systolic blood pressure between the two subsets on postnatal day 1 (FGR 52+/-6 mmHg vs. normal 46+/-4 mmHg) and day 5 (FGR 76+/-5 mmHg vs. normal 60+/-6 mmHg). CONCLUSION: Left ventricular isovolumic relaxation time may act as a sensitive index of increased arterial afterload in the growth retarded fetus and may herald raised systolic blood pressure in the early neonatal period.
