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1.
Yi Chuan ; 45(1): 29-41, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36927636

RESUMEN

Hereditary deafness is one of the most common sensory disorders in humans, and exhibits high genetic heterogeneity. At present, the commonly used molecular diagnostic methods include gene chip, Sanger sequencing, targeted enrichment sequencing, and whole-exome sequencing, with diagnosis rates reaching 33.5%-56.67%. However, there are still a considerable number of patients who can not get a timely and definitive molecular diagnosis. Furthermore, considering the economic burden on patients' families and the relatively high cost of whole-exome or whole-genome sequencing, it is vital to provide stepwise strategies combining multiple detection methods according to the phenotypes of patients. In this review, we evaluate and discuss the utility of molecular diagnosis and the application of stepwise testing strategies in hereditary deafness to provide reference for the selection of diagnostic strategies.


Asunto(s)
Sordera , Humanos , Sordera/diagnóstico , Sordera/genética , Secuenciación Completa del Genoma , Exoma , Fenotipo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Linaje , Pruebas Genéticas , Mutación
2.
BMC Nephrol ; 22(1): 83, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33691640

RESUMEN

BACKGROUND: Primary hyperoxaluria(PH)is a rare autosomal recessive genetic disease that contains three subtypes (PH1, PH2 and PH3). Approximately 80% of PH patients has been reported as subtype PH1, this subtype of PH has been related to a higher risk of renal failure at any age. Several genetic studies indicate that the variants in gene AGXT are responsible for the occurrence of PH1. However, the population heterogeneity of the variants in AGXT makes the genetic diagnosis of PH1 more challenging as it is hard to locate each specific variant. It is valuable to have a complete spectrum of AGXT variants from different population for early diagnosis and clinical treatments of PH1. CASE PRESENTATION: In this study, We performed high-throughput sequencing and genetic analysis of a 6-year-old male PH1 patient from a Chinese family. Two variants (c.346G > A: p.Gly116Arg; c.864G > A: p.Trp288X) of the gene AGXT were identified. We found a nonsense variant (c.864G > A: p.Trp288X) that comes from the proband's mother and has never been reported previously. The other missense variant (c.346G > A: p.Gly116Arg) was inherited from his father and has been found previously in a domain of aminotransferase, which plays an important role in the function of AGT protein. Furthermore, we searched 110 pathogenic variants of AGXT that have been reported worldwide in healthy local Chinese population, none of these pathogenic variants was detected in the local genomes. CONCLUSIONS: Our research provides an important diagnosis basis for PH1 on the genetic level by updating the genotype of PH1 and also develops a better understanding of the variants in AGXT by broadening the variation database of AGXT according to the Chinese reference genome.


Asunto(s)
Codón sin Sentido , Hiperoxaluria Primaria/genética , Transaminasas/genética , Pueblo Asiatico/genética , Niño , China , Genoma , Humanos , Masculino , Linaje
3.
Otolaryngol Head Neck Surg ; 127(3): 138-44, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12297801

RESUMEN

OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.


Asunto(s)
Deleción Cromosómica , ADN Mitocondrial/efectos de los fármacos , Modelos Animales de Enfermedad , Fosfatidilcolinas/uso terapéutico , Presbiacusia/tratamiento farmacológico , Presbiacusia/genética , Administración Oral , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , ADN Mitocondrial/genética , Evaluación Preclínica de Medicamentos , Potenciales Evocados Auditivos del Tronco Encefálico , Citometría de Flujo , Potenciales de la Membrana , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacología , Reacción en Cadena de la Polimerasa , Presbiacusia/diagnóstico , Distribución Aleatoria , Ratas , Ratas Endogámicas F344
4.
PLoS One ; 9(2): e89240, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24586623

RESUMEN

TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic deafness (designated DFNA) or as the autosomal-recessive version. The α-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Using targeted DNA capture and massively parallel sequencing (MPS), we screened 42 genes known to be responsible for human deafness in a Chinese family (Family 3187) in which common deafness mutations had been ruled out as the cause, and identified a novel mutation, c.257-262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA gene in the proband and his extended family. All affected individuals in this family had moderate down-sloping hearing loss across all frequencies. To our knowledge, this is the second TECTA mutation identified in Chinese population. This study demonstrates that targeted genomic capture, MPS, and barcode technology might broaden the availability of genetic testing for individuals with undiagnosed DFNA.


Asunto(s)
Sordera/genética , Proteínas de la Matriz Extracelular/genética , Mutación , Pueblo Asiatico/genética , Audiometría de Tonos Puros , China , Análisis Mutacional de ADN , Sordera/fisiopatología , Femenino , Proteínas Ligadas a GPI/genética , Humanos , Masculino , Linaje , Embarazo , Diagnóstico Prenatal
5.
Ying Yong Sheng Tai Xue Bao ; 19(3): 545-50, 2008 Mar.
Artículo en Zh | MEDLINE | ID: mdl-18533523

RESUMEN

The study on the size distribution of water-stable aggregates (WSAs) in calcic kastanozem of Loess Plateau after 27 years fertilization showed that compared with those of natural soil, the contents of > 0.25 mm WSAs in 0-10 cm and 10-20 cm layers of cultivated soil decreased by 21.35% and 38.82%, respectively, and those of > or = 0.5 mm WSAs also had a decreasing trend, with the greatest decrement of > 5 mm and 5-2 mm WSAs. On the contrary, the contents of 0.5-0.25 mm WSAs in the two soil layers increased by 104.75% and 23.13%, respectively. All sizes WSAs had higher contents in 0-10 cm than in 10-20 cm soil layer. Fertilization had remarkable effects on the formation of WSAs. Under the applications of organic manure and its combination with chemical fertilizers, the content of 5-2 mm WSAs increased most, followed by that of > 5 mm WSAs. After applying organic manure, organic manure plus chemical fertilizers, and straws, the contents of larger sizes WSAs increased significantly, being beneficial to the improvement of soil structure. In all fertilization treatments, the mean mass diameter (MMD) of WSAs was larger in 0-10 cm than in 10-20 cm soil layer. Compared with non-fertilization, long-term fertilization increased the MMD of WSAs, and organic manure was superior to chemical fertilizers. The MMD of WSAs was positively correlated with the amount of > 0.25 mm WSAs.


Asunto(s)
Fertilizantes , Suelo/análisis , Movimientos del Agua , Agua/análisis , China , Productos Agrícolas/crecimiento & desarrollo , Tamaño de la Partícula , Factores de Tiempo
6.
J Neurochem ; 85(4): 911-24, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12716423

RESUMEN

Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in brain regions associated with drug reinforcement. To evaluate whether the alterations in gene expression in cocaine overdose victims are associated with specific dopamine populations in the midbrain, cDNA arrays and western blotting were used to compare gene and protein expression patterns between cocaine overdose victims and age-matched controls in the ventral tegmental area (VTA) and lateral substantia nigra (l-SN). Array analysis revealed significant up-regulation of numerous transcripts in the VTA, but not in the l-SN, of cocaine overdose victims including NMDAR1, GluR2, GluR5 and KA2 receptor mRNA (p < 0.05). No significant alterations between overdose victims and controls were observed for GluR1, R3 or R4 mRNA levels. Correspondingly, western blot analysis revealed VTA-selective up-regulation of CREB (p < 0.01), NMDAR1 (p < 0.01), GluR2 (p < 0.05), GluR5 (p < 0.01) and KA2 (p < 0.05) protein levels of cocaine overdose victims. The present results indicate that selective alterations of CREB and certain ionotropic glutamate receptor (iGluR) subtypes appear to be associated with chronic cocaine use in humans in a region-specific manner. Moreover, as subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine in humans.


Asunto(s)
Cocaína/envenenamiento , Dopamina , Perfilación de la Expresión Génica , Mesencéfalo/química , Mesencéfalo/efectos de los fármacos , Adulto , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/análisis , Dopamina/fisiología , Sobredosis de Droga , Femenino , Proteínas de Unión al GTP/análisis , Humanos , Masculino , Mesencéfalo/patología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Procesamiento Postranscripcional del ARN/efectos de los fármacos , ARN Mensajero/análisis , ARN Mensajero/genética , Receptores AMPA/genética , Receptores de Ácido Kaínico/genética , Receptores de N-Metil-D-Aspartato/genética , Transducción de Señal/efectos de los fármacos , Sustancia Negra/química , Sustancia Negra/efectos de los fármacos , Sustancia Negra/patología , Regulación hacia Arriba/efectos de los fármacos , Área Tegmental Ventral/química , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/patología
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