RESUMEN
OBJECTIVE@#To detect potential variation in glutaryl-CoA dehydrogenase (GCDH) gene among three Chinese families affected with glutaric acidemia type Ⅰ(GA-1) and correlate the genotypes with phenotypes.@*METHODS@#Genomic DNA was extracted from peripheral blood samples derived from three patients with GA-1 and their family members. The coding regions of the GCDH gene were amplified with PCR and subjected to Sanger sequencing.@*RESULTS@#The clinical manifestation of the patients varied from macrocephaly to severe encephalopathy, with notable phenotypic difference between siblings carrying the same variation. In pedigrees 1 and 2, the probands have carried compound heterozygous variations c.1133C>T(p.Ala378Val) and c.1244-2A>C, which were derived their fathers and mothers, respectively. In pedigree 3, the proband has carried compound heterozygous variation c.339delT (p.Tyr113) and c.406G>T (p.Gly136Cys). Among these, variations c.339delT and c.1133C>T were verified as novel by retrieval of dsSNP, HGMD and 1000 genome database. Bioinformatic analysis suggested that above variations can affect protein function and are probably pathogenic.@*CONCLUSION@#Above discovery has expanded the mutation spectrum of the GCDH gene. No correlation was found between the clinical phenotype and genotype of GA-1 patients.
Asunto(s)
Humanos , Errores Innatos del Metabolismo de los Aminoácidos , Diagnóstico , Genética , Encefalopatías Metabólicas , Diagnóstico , Genética , China , Análisis Mutacional de ADN , Glutaril-CoA Deshidrogenasa , Genética , MutaciónRESUMEN
MicroRNAs (miRNAs), with 19-25 nucleotides in length, are small non-coding single-stranded RNAs and play an important role in a variety of organisms cell growth, differentiation, proliferation and apoptosis, fat metabolism and other physiological processes. Numerous studies have shown that the deregulation of miRNAs was associated with progression, prognosis and drug resistance of chronic lymphocytic leukemia (CLL). MiR-15a/16-1 cluster, miRs-34b/c , miR-181b, miR-29, miR-3676, miR-17/92 and miR-155 family members were the most common deregulated miRNAs in CLL, which could regulate important gene expressions. To further clarify molecular mechanism of occurrence and development of CLL, this review focuses on recent advances on the regulatory networks of related miRNAs as well as the integration with other regulators.
RESUMEN
<p><b>OBJECTIVE</b>To review the clinical features of a families affected with glutaric acidemia type I (GA-1) and screen potential mutations in glutaryl-CoA dehydrogenase (GCDH) gene.</p><p><b>METHODS</b>Clinical data of the patients and their family members was analyzed. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Two patients have manifested macrocephaly. Imaging analysis revealed arachnoid cyst and subdural effusion. The elder sister had encephalopathy crisis. The younger sister had significantly raised glutaric acid, whilst the elder sister was normal during the non-acute phase. Genetic analysis has revealed a homozygous c.1244-2A> C mutation of the GCDH gene in both patients.</p><p><b>CONCLUSION</b>The clinical features and mutation of the GCDH gene have been delineated in a Chinese family affected with GA-1. The c.1244-2A> C mutation may be particularly common in the Chinese population.</p>