RESUMO
OBJECTIVE: To screen potential mutations of PHEX gene in a family featuring hypophosphatemic rickets in order to confirm the molecular diagnosis and pathogenetic mechanism. METHODS: Genomic DNA was extracted from peripheral venous blood samples. DNA sequence of PHEX gene was derived from UCSC database, and primers for its coding region were designed with Primer premier 5.0. Potential mutations were detected with PCR amplification and DNA sequence analysis. RESUTLS: A mutation was identified in intron 6 of the PHEX gene in the proband and his mother. CONCLUSION: The c.732+1G>T mutation underlies the hypophosphatemic rickets in this family.
Assuntos
Hipofosfatasia/enzimologia , Hipofosfatasia/genética , Mutação , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Adulto , Sequência de Bases , Criança , Feminino , Humanos , Íntrons , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
Recently, several TARDBP mutations have been identified in sporadic amyotrophic lateral sclerosis (SALS) patients among different ethnicities. Our study aims to analyze the clinical features and mutations in the TARDBP gene among Chinese patients with SALS. One hundred sixty-five patients were studied. The mean age of onset was 50.8±12.0 years. The mean diagnostic delay was 18.8±17.1 months. A novel missense mutation (p.N378S) and a novel silent change (p.A321A) were detected in 2 male patients, respectively. A new variant of c.1098C>G in exon 6 and 2 reported variants, g.IVS1+85C>T in intron 1 and c.57A>G in exon 2, were found. The frequency of the "G" variant of c.57A>G in exon 2 and the "G" variant of c.1098C>G in exon 6 were significantly lower in the patient group than in the control (p=0.001 and p=0.024, respectively). Our findings provide first evidence that the frequency of TARDBP gene mutations is rare among Chinese SALS patients (0.61%). Several polymorphisms may influence susceptibility to amyotrophic lateral sclerosis.
Assuntos
Esclerose Lateral Amiotrófica/genética , Povo Asiático/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Mutação/genética , Adulto , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/etnologia , China/epidemiologia , Feminino , Predisposição Genética para Doença/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Dopa-responsive dystonia (DRD) is typically caused by heterozygous mutations in GTP cyclohydrolase 1 gene (GCH1). Our aim was to investigate the clinical and genetic features of Chinese DRD patients. We analyzed a cohort of Chinese DRD patients' clinical data. Mutation of the GCH1 gene was screened by direct sequencing. Additionally, multiplex ligation-dependent probe amplification (MLPA) assay targeting the GCH1 and the TH gene to evaluate large exon deletion or duplicate mutation of the genes were performed in point mutation-negative patients. Ten sporadic DRD patients and two pedigrees including six patients were included in the study. The onset age ranged from 3 to 15 years old. All patients initially presented with walking problems due to lower limb dystonia. The delay between onset and diagnosis ranged from 1 to 42 years old. The symptoms were completely or near-completely abolished with low dose levodopa treatment (dosages ranged from 25 mg to 400 mg/day). Direct sequencing in 14 patients found two known mutations (Gly203Arg in exon 5 in four unrelated patients and Met102Lys in exon 1 in one patient) and one new mutation (Thr186Ile mutation in exon 5 in two unrelated pedigrees). A heterozygous exon 2 deletion in the GCH1 gene was found in one of three point mutation-negative patients by MLPA analysis. Our clinical findings in DRD patients were consistent with other studies. GCH1 gene mutations were quite common in Chinese patients. MPLA should be performed in routine deletion analysis of GCH1 in point mutation-negative DRD patients.
Assuntos
Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Agonistas de Dopamina/uso terapêutico , Distonia , GTP Cicloidrolase/genética , Levodopa/uso terapêutico , Mutação Puntual/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Primers do DNA/genética , Agonistas de Dopamina/administração & dosagem , Distonia/tratamento farmacológico , Distonia/etnologia , Distonia/genética , Éxons/genética , Feminino , Humanos , Lactente , Levodopa/administração & dosagem , Masculino , Linhagem , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
OBJECTIVE: To investigate the distribution characteristics of Y chromosome haplogroups in Sichuan Han population. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), denatured high performance liquid chromatography (DHPLC) and DNA sequencing methods, 18 Y-chromosome bialletic markers were detected to type Y chromosome haplogroups in 341 unselected men from Sichuan Han population. RESULTS: A total of 14 haplogroups were observed, in which haplogroups H2 and H4 were identified for the first time in Sichuan population, and haplogroups H14 and N* were found firstly in Chinese. There was a significant frequency difference of Y haplogroups between Sichuan Han population and Southern Han population. CONCLUSION: More comprehensive frequency distribution data of Y chromosome haplogroups are obtained in Sichuan Han population, which would be helpful for understanding the association of Y chromosome background and the susceptibility to male specific diseases such as spermatogenic failure, prostate cancer, testical cancer and so on in present population.
