RESUMEN
OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a Chinese pedigree with Lesch-Nyhan syndrome (LNS) but no specimen from the affected probands. METHODS: All affected individuals in this pedigrees were male and had deceased during childhood, with no biological specimen left. Based on their typical neurological dysfunction and tendency for self-mutilation, the diagnosis of LNS was suspected. Sanger sequencing was carried out to detect potential variant of the HPRT1 gene among female members from the pedigree. Following the identification of the pathogenic variant, prenatal diagnosis was provided for a high-risk fetus. RESULTS: The proband's mother and three other females were found to harbor heterozygous c.500_501delGGinsC (p.Arg167fs*23) variant of the HPRT1 gene, which was unreported previously. Prenatal diagnosis showed that the fetus was a male and had inherited the same pathogenic variant. CONCLUSION: The c.500_501delGGinsC variant of the HPRT1 gene probably underlay the LNS in this pedigree. Above finding has provided a basis for prenatal diagnosis and genetic counseling for this pedigree.
Asunto(s)
Síndrome de Lesch-Nyhan , Masculino , Femenino , Humanos , Embarazo , Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/genética , Linaje , Hipoxantina Fosforribosiltransferasa/genética , Diagnóstico Prenatal , China , MutaciónRESUMEN
OBJECTIVE: To investigate the effect of ascorbic acid (VC) on relaxation of ex vivo Bufo gastrocnemius during sustained isometric contraction. METHODS: Dynamic tension of the muscle was recorded under constant voltage stimulation within 7.0 min at 2 s intervals. The rest tension and relaxation rate of the muscle was obtained by weighted fitting to the relaxation process of tension <90% of its peak with a mono-exponential model to characterize the muscular relaxation. RESULTS: VC at 2.0 mmol/L alone or in combination with the inhibitors of the antixoidation enzymes (surperoxide dismutase, glutathione peroxidase and catalase) resulted in negligible alterations in the muscular relaxation kinetics. VC combined with the inhibitor of surperoxide dismutase resulted in significantly lowered relaxation rate while increased rest tension, but VC with the inhibitor of either catalase or glutathione peroxidase showed negligible action. VC combined with the inhibitors of all the 3 enzymes also caused significant effect on the muscular relaxation kinetics, which was similar the effect of VC with superoxide dismutase inhibitor. CONCLUSION: VC at high concentration may result in oxidative toxicity to the biological system rich in transitional metal ion complexes but with low antioxidation capacity by causing superoxide-mediated oxidative damages.
Asunto(s)
Ácido Ascórbico/farmacología , Contracción Isométrica/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Animales , Bufonidae , Estimulación Eléctrica , Técnicas In Vitro , Músculo Esquelético/fisiologíaRESUMEN
OBJECTIVE: To characterize the isometric contractility of Bufo gastrocnemius ex vivo in light of the rest tension. METHODS: Bufo gastrocnemius treated with SOD inhibitor and ascorbate was stimulated electrically (12 V DC, 2 ms duration with a 2 s interval) to record the tension within 10 min. Weighted fitting to the relaxation curve of the tension below 90% of the peak tension with a mono-exponential model yielded the rest tension and relaxation rate. RESULTS: The control gastrocnemius showed monotonic decrease of the rest tension, but treatment with SOD inhibitor and ascorbate resulted in a decrease of the rest tension followed by a fast increase within a 1.0 min contraction. The increase of the rest tension at 7.0 min of contraction of the treated muscle was significantly greater than that of the control muscle. The control muscle showed a monotonic decrease of the relaxation rate in 10 min, whereas treatment with SOD inhibitor and ascorbate produced increased relaxation rate followed by monotonic decrease till a plateau was reached. In the course of the 10 min recording, the relaxation rate of the treated muscle was lower than that of the control after the same duration of contraction. CONCLUSION: Rest tension is a characteristic index to represent the skeletal muscle contractility.