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Objective: To assess the role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. Design: Published studies of hepatitis C transmission were examined. Twenty nine studies with identified sources of hepatitis C infection who were tested for presence of hepatitis C RNA by polymerase chain reaction were reviewed, including studies of vertical transmission (n = 21), transmission after transplantation (n = 3), transfusion of blood components (n = 3), and needlestick exposure (n = 2). Subjects: All patients identified in studies. Results: A total of 2022 people who had been exposed to sources positive for antibody to hepatitis C were identified. Among 1148 people exposed to sources positive by polymerase chain reaction 148 cases of transmission occurred compared with no definite case among 874 people exposed to negative sources. Rates of transmission from positive sources were 6.2% for perinatal exposure, 6.1% after needlestick exposure, 78% after solid organ or bone marrow transplantation, and 83% after transfusion of blood components. Other factors influencing risk of vertical transmission were coinfection with HIV and level of hepatitis C viraemia. Conclusions: Negative results by polymerase chain reaction indicate an extremely low probability of transmission of hepatitis C from a person with antibody to hepatitis C.

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Methylmalonyl-CoA mutase (MCM) apoenzyme deficiency is a rare metabolic disease that may result in distinct biochemical phenotypes of methylmalonic acidemia (MMA), namely mut(o) and mut-. We analyzed a cohort of 40 MCM-deficient patients with MMA affected by either the mut(o) or the mut- form of the disease. By direct sequencing of cDNA and gDNA of the MUT gene, we detected 42 mutations, 29 of which were novel mutations. These included five frameshift mutations (insertion, deletion, or duplication of a single nucleotide), five sequence modifications in consensus splice sites, six nonsense and 12 missense mutations, and a large genomic deletion including exon 12. We explored how the 12 novel missense mutations might cause the observed phenotype by mapping them onto a three-dimensional model of the human MCM generated by homology with the P. shermanii enzyme. In this work we update the spectrum of MCM mutations (n=84), and then discuss their prevalence and distribution throughout the coding sequence in relation to the enzyme structure.