RESUMEN
BACKGROUND: We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. METHODS: In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. RESULTS: One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. CONCLUSIONS: The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.
Asunto(s)
Niño , Preescolar , Humanos , Masculino , Pueblo Asiatico/genética , ADN/síntesis química , Exones , Glucosafosfato Deshidrogenasa/química , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Mutación Missense , Polimorfismo Genético , Estructura Terciaria de Proteína , República de Corea , Análisis de Secuencia de ADNRESUMEN
The main purpose of this report is to describe nine cases of xeroderma pigmentosum with primary spontaneous corneal scarring in the absence of history of corneal ulcers or infectious keratitis. The authors studied nine patients with xeroderma pigmentosum. Each patient underwent complete ophthalmologic and dermatologic examinations. Three patients underwent excision of squamous cell carcinoma of the conjunctiva. There were five male and four female patients, with a mean age of 14 years and a range of 5 to 21 years. Seven had conjunctival squamous cell carcinoma. All patients had spontaneous diffuse corneal stromal scars without clinical evidence of keratitis and no previous history of corneal ulcer. The corneal sensation was intact. None of the patients had ulceration of the cornea. One patient had dry eye syndrome. The clinical and histopathologic changes of the cornea and conjunctiva in patients with xeroderma pigmentosum appear to be similar to the changes occurring in sun-exposed skin. This suggests that direct exposure of corneal and conjunctival tissue to ultraviolet light in patients with xeroderma pigmentosum is the primary cause of scarring in the cornea and conjunctiva, which leads to loss of vision
Asunto(s)
Córnea/patología , Oftalmología , ADN/síntesis químicaRESUMEN
En el presente trabajo se evalúa la presunta capacidad inductora de Síntesis no programada de ADN(SNP de ADN) del interferón alfa leucocitario, utilizando la línea celular RAJI(linfoma de Burkitt), incluyéndose la realización de un enzayo de citotoxicidad de las concentraciones seleccionadas (1 400,700,350,175 UI/ml). No se detectó capacidad inductora de SNP de ADN, ni actividad citotóxica en el rango de concentraciones empleado