RESUMEN
OBJECTIVE: Determine the frequency of mutations in exon 8 of ATP7B gene. MATERIAL AND METHOD: The exon 8 of ATP7B gene in twenty 20 unrelated Thai patients with Wilson disease (WD) was analyzed RESULTS: Three heterozygous mutations were identified in four patients. The Arg778Leu (G2333T) and 2299insC mutations have been previously reported. The authors also identified a novel missense mutation, Thr766Arg (C2297G). Despite the Arg778Leu mutation being common in East Asian populations, its frequency in Thais was only 5% in the presented patients. CONCLUSION: Sequencing of the exon 8 of the ATP7B gene is insufficient for the diagnostic service testing in Thais.
Asunto(s)
Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Exones , Degeneración Hepatolenticular/genética , Mutación Missense , Adenosina Trifosfatasas/metabolismo , Adolescente , Adulto , Pueblo Asiatico/genética , Proteínas de Transporte de Catión/metabolismo , Niño , ATPasas Transportadoras de Cobre , Análisis Mutacional de ADN , Femenino , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/etnología , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Tailandia , Adulto JovenAsunto(s)
Efecto Fundador , Frecuencia de los Genes/genética , Variación Genética/genética , Genética de Población , Mutación , Enfermedad de Parkinson/genética , Anciano , China/etnología , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/genética , Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , TailandiaRESUMEN
Spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders with almost 30 subtypes. The prevalence and relative frequency of each subtype vary among different populations. In this article, we report the relative frequency of six SCA subtypes in the Thai population and attempt to explain the observed pattern when compared with other populations in this region. We searched for SCA type 1, SCA2, SCA3, SCA6, SCA7 and dentatorubral-pallidoluysian atrophy mutations using GeneScan analysis in 340 patients from 182 families, in which at least one person had a clinical diagnosis of SCA. We analyzed the relative frequencies of SCA subtypes on a family basis, and compared these with the data in the Chinese and Indian populations. SCA3 was found in 19.2% of the patients (Agresti-Coull 95% confidence interval: 14.1-25.6%), SCA1 in 11.5% (7.6-17.1%) and SCA2 in 10.4% (6.7-15.8%). SCA6 was found in three families, with a relative frequency of 1.6% (0.3-5.0%). Compared with the related populations, the Thai SCA3 frequency was less than that of the Chinese, whereas it was higher than that in most of the Indian studies. The reverse is true for the SCA1/SCA2 frequency. A similar study in Singapore, where there was a clear history of population admixture, also showed the frequencies between those of the Chinese and the Indian populations. Although SCA3 was the most common identifiable SCA subtype in Thailand, SCA1 and SCA2 were also relatively common. Our results also supported some degree of admixture with the Indians in the Thai population and justify further study in the area.
Asunto(s)
Genética de Población , Ataxias Espinocerebelosas/clasificación , Ataxias Espinocerebelosas/epidemiología , Geografía , Humanos , Tailandia/epidemiologíaRESUMEN
BACKGROUND: Duchenne muscular dystrophy (DMD), a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD), are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations. METHODS: We reviewed our database for the detection of Dystrophin gene mutation by means of 31-exon multiplex PCR in Thai males, diagnosed clinically and biochemically with DMD or BMD from July 1994 to November 2006. One index patient was chosen from each family for statistical analysis. The overall sensitivity of the test, the number of fragment deleted, and the deletion frequency of each fragment were calculated, along with their 95% confidence intervals (C.I.). RESULTS: We found deletions in 99 out of the 202 index patients (49%; Bayesian 95% C.I.=42%-56%). 51% of these had deletion in only one of the 31 exons tested, while the patient with the most extensive deletions had 14 exons deleted. The mean number of deleted exons were 2.84 (BC(a) bootstrap 95% C.I.=2.37-3.48), or 5.02 (3.81-6.85) if all the untested exons adjacent to the confirmed deleted exons were assumed to be deleted. The region spanning exons 44-52 was the most frequently deleted. These were similar to those reported in the Japanese. CONCLUSION: The multiplex PCR detected deletions only in about half of the Thai patients. The diseases therefore should not be excluded solely on the negative result if DMD/BMD is strongly suspected.
Asunto(s)
Distrofina/genética , Distrofia Muscular de Duchenne/genética , Mutación/genética , Reacción en Cadena de la Polimerasa/métodos , Diagnóstico Diferencial , Humanos , Masculino , Distrofia Muscular de Duchenne/diagnóstico , Pronóstico , Sensibilidad y EspecificidadRESUMEN
Haemoglobin (Hb) Hope [beta136(H14)Gly-->Asp(GGT-->GAT)] is one of the unstable haemoglobin variants of the beta-globin chain, which is demonstrated in people of various ethnic backgrounds. Here we report a Thai female patient with clinical thalassaemia intermedia since childhood. This patient had experienced neither blood transfusion nor hospitalisation. Hb Bart's-H and a large amount of Hb Hope were identified by high-performance liquid chromatography (HPLC) assay and the diagnosis of homozygous Hb Hope was definitely achieved by direct sequencing of exon 3 of beta-globin gene. Furthermore, we could identify that her brother carried the mutation of homozygous Hb Hope without abnormal alpha globin chain involvement, and another family member had heterozygous Hb Hope in association with -alpha(3.7) mutation, and both of them were clinically silent.
Asunto(s)
Hemoglobina H/genética , Hemoglobinopatías/genética , Hemoglobinas Anormales/genética , Talasemia alfa/genética , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Globinas/genética , Hemoglobinopatías/diagnóstico , Homocigoto , Humanos , Tailandia , Talasemia alfa/diagnósticoRESUMEN
We report on a Thai female patient who presented with hypochromic microcytic anemia, hepatosplenomegaly, and failure to thrive since 3 years of age. Hematological and hemoglobin (Hb) analysis were consistent with a clinical diagnosis of Hb H disease. However, no abnormal Hb fraction had ever been detected. During the 20 years of follow-up, this patient experienced several episodes of hemolytic crisis, which worsened her anemia, necessitating blood transfusion. Recently, we identified Hb Quong Sze (Hb QS), a highly unstable globin gene mutation affecting codon 125 (CTG-->CCG) of alpha(2) globin gene in trans with the commonest alpha(0) thalassemia (-(SEA)) in the patient. This report highlights the clinical significance of Hb QS in Southeast Asians, as previously almost all of the patients described with this variant were of Chinese origin.