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>

The study of SLC12A3 complicated heterozygotic mutation in Children Gitelman syndrome / 医学研究生学报

Objective Gitelman Syndrome is a disease caused by the mutation of Na-Cl cotransporter gene(SLC12A3).The article studied the significance of diagnosis and identification by genetic mutation. Methods We collected the clinical data, then we sequenced the SLC12A3 gene by the first sequencing technology and MLPA. Results SLC12A3 complicated heterozygotic mutation was observed.One of them showed c.1964G>A, p.(Arg655His) and exon 8 deletion mutation, the other showed c.2543A>T, p.(Asp848Val) and c.976delG, p.(Val326fs) mutation of SLC12A3 gene in children. Conclusion The final diagnosis depended on gene diagnosis. Pediatrician must recognize the manifestations to advoid misdiagnosis.

Clinical investigation and genetic analysis of a Chinese family with glutaric acidemia type I / 中华医学遗传学杂志

<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>