Clinical and variation analysis of three Chinese families affected with glutaric acidemia type 1 / 中华医学遗传学杂志

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.

Analysis of clinical features and genetic mutations in a Chinese family affected with Menkes disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the clinical features and potential mutation of the ATP7A gene in a family affected with Menkes disease.</p><p><b>METHODS</b>Clinical data of a patient and his family members were analyzed. Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assays were performed to detect the mutation of the ATP7A gene.</p><p><b>RESULTS</b>The patient was admitted at the age of 5 months due to severe epilepsy and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were noted. Cranial magnetic resonance imaging and angiography revealed cortical atrophy, leukoencephalopathy and circuitous of intracranial vessels. The plasma ceruloplasmin was decreased. MLPA has identified a deletion spanning exons 8 to 12 of the ATP7A gene. His mother was found to be a heterozygous carrier of the same mutation.</p><p><b>CONCLUSION</b>The clinical features and a novel mutation of the ATP7A gene of the family have been delineated.</p>