A novel mutation (C271F) in the Notch3 gene in a Chinese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset hereditary condition caused by mutations in the Notch3 gene. A Chinese man was studied. METHOD: Electronic microscopy examination of skin biopsy. The Notch3 gene was screened for mutations by polymerase chain reaction and direct DNA sequencing. RESULTS: Electronic microscopy showed the presence of deposits of granular osmiophilic material in dermal capillaries in the index patient. A novel heterozygous C271F in exon 6 was detected in the index patient. This heterozygous C271F mutation was also detected in the asymptomatic elder son but was not detected in the asymptomatic wife of the patient. Allele specific amplification showed that C271F was not detected in 100 normal subjects. CONCLUSION: We established the molecular basis of CADASIL in a Chinese man. Mutation detection assay provides a reliable method for confirming the diagnosis of CADASIL.

Novel mutations in the BCHE gene in patients with no butyrylcholinesterase activity.

BACKGROUND: Butyrylcholinesterase (BCHE) deficiency is characterized by prolonged apnea after the use of certain muscle relaxants with the genetic defect lying in the BCHE gene. METHODS: Two Chinese patients with no serum BCHE activity were studied. The BCHE genes were screened for mutations by polymerase chain reaction and direct DNA sequencing. RESULTS: Of the four mutations detected, two novel mutations were identified in the two patients, i.e., F474L, and an insertion of an adenine between nucleotide positions 395 and 396. This information was used to screen the immediate families of the patients for carrier status. CONCLUSIONS: We established the molecular basis of butyrylcholinesterase deficiency in two Chinese patients. The developed mutation detection assay provides a reliable method for identifying mutant BCHE carriers.

Diagnostic value of pleural fluid adenosine deaminase activity in tuberculous pleurisy.

BACKGROUND: Diagnosis of tuberculous pleuritis is difficult because of its nonspecific clinical presentation and insufficient efficiency of traditional diagnostic methods. We investigated the use of adenosine deaminase (ADA) activity in tuberculous pleuritis diagnosis. METHODS: We optimized a kinetic assay and retrospectively analysed 210 patients with exudative pleural effusions. Using the ROC curve, we determined the optimal cutoff for TB pleurisy. RESULTS: One hundred forty-seven exudative samples were nontuberculous (non-TB) and 63 were tuberculous (TB). There was statistically significant difference (p<0.0001) between the means of pleural fluid ADA levels among the TB and non-TB populations. The disease prevalence of TB pleurisy in the studied population was 30%. The cutoff value for diagnosing TB effusions was >55.8 U/L, with a sensitivity of 87.3% (95% CI: 76.5-94.3%) and specificity of 91.8% (95% CI: 86.2-95.7%). The positive predictive value (PPV) was 82.1% and the negative predictive value (NPV) was 94.4%. A pleural fluid ADA value <16.81 IU/L suggests that a tuberculous effusion is highly unlikely (100% sensitive with 100% NPV and 0% negative likelihood ratio for a pleural fluid ADA level>/=16.81 U/L). In addition, the area under the ROC curve was 0.933 (S.E.=0.0230, 95% CI: 0.890-0.963). CONCLUSION: Pleural fluid total ADA assay is a sensitive and specific test suitable for rapid diagnosis of TB pleurisy.

Mitochondrial DNA deletion in a girl with Fanconi's syndrome.

We report a sporadic large-scale mitochondrial deletion in a paediatric patient with Fanconi's syndrome. Renal biopsy disclosed chronic interstitial nephritis. Ultrastructural examination of the renal tissue showed many giant atypical mitochondria. Histochemical stains revealed markedly reduced cytochrome c oxidase (COX). Genetic analysis disclosed a novel mitochondrial deletion of 7.3 kb in both peripheral blood and renal tissue. Mitochondrial diseases have heterogeneous clinical phenotypes; mutation analysis has proved to be an effective tool in confirming the diagnosis.