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Beatriz Puisac, Mónica Ramos,
María Arnedo,
Sebastián Menao,
María Concepción Gil-Rodríguez,
María Esperanza Teresa-Rodrigo,
Angeles Pié,
Juan Carlos de Karam,
Jan-Jaap Wesselink,
Ignacio Giménez,
Feliciano J Ramos,
Nuria Casals,
Paulino Gómez-Puertas,
Fausto G Hegardt,
Juan Pié
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ABSTRACT: The genes HMGCS2 and HMGCL encode the two main enzymes for ketone-body synthesis, mitochondrial HMG-CoA synthase and HMG-CoA lyase. Here, we identify and describe possible splice variants of these genes in human tissues. We detected an alternative transcript of HMGCS2 carrying a deletion of exon 4, and two alternative transcripts of HMGCL with deletions of exons 5 and 6, and exons 5, 6 and 7, respectively. All splice variants maintained the reading frame. However, Western blot studies and overexpression measurements in eukaryotic or prokaryotic cell models did not reveal HL or mHS protein variants. Both genes showed a similar distribution of the inactive variants in different tissues. Surprisingly, the highest percentages were found in tissues where almost no ketone bodies are synthesized: heart, skeletal muscle and brain. Our results suggest that alternative splicing might coordinately block the two main enzymes of ketogenesis in specific human tissues.
Molecular Biology Reports 09/2011; 39(4):4777-85. · 2.93 Impact Factor
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Doris Gallegos,
Andrea Olea,
Viviana Sotomayor,
Claudia González,
Juan Carlos Muñoz, Mónica Ramos,
M Cecilia Espinoza,
Gladys Mendoza,
Graciela Torres,
Emilio Espiñeira,
Winston Andrade,
Jorge Fernández,
Rodrigo Fasce
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ABSTRACT: Strategies for accelerated control of rubella and congenital rubella syndrome (CRS) in Chile included mass vaccination of women of childbearing age in 1999 but did not include vaccination of adult men.
We reviewed data from Chile's integrated surveillance system for measles, rubella, and CRS from 2004 through 2009 and describe the epidemiology of rubella outbreaks and implementation of control measures in 2005 and 2007 following mass vaccination of women. Population estimates from census data were used to calculate rubella incidence rates. The age distribution of rubella cases during 2007 was compared with rubella vaccination opportunities by birth cohort to orient mass vaccination of adult men.
In 2005, an institutional outbreak of rubella occurred among male naval recruits 18-22 years of age, with 46 confirmed cases over a 5-month period. Beginning in March 2007, rubella outbreaks among young adults in the capital of Santiago spread throughout Chile, resulting in >4000 confirmed rubella cases. Delayed control measures and rapid dissemination among young adults led to widespread transmission. From 2007 through 2009, rubella incidence was highest among adult men not included in previous vaccination strategies. Mass vaccination of men 19-29 years of age was conducted in November 2007 to interrupt rubella transmission.
Chile's experience suggests that vaccination strategies for rubella and CRS elimination need to include both men and women.
The Journal of Infectious Diseases 09/2011; 204 Suppl 2:S669-74. · 6.41 Impact Factor
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Sebastián Menao,
Eduardo López-Viñas,
Cecilia Mir,
Beatriz Puisac,
Esther Gratacós,
María Arnedo,
Patricia Carrasco,
Susana Moreno, Mónica Ramos,
María Concepción Gil, [......],
Magdalena Ugarte,
Peter T Clayton,
Stanley H Korman,
Dolors Serra,
Guillermina Asins,
Feliciano J Ramos,
Paulino Gómez-Puertas,
Fausto G Hegardt,
Nuria Casals,
Juan Pié
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ABSTRACT: 3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder that affects ketogenesis and L-leucine catabolism. The clinical acute symptoms include vomiting, convulsions, metabolic acidosis, hypoketotic hypoglycaemia and lethargy. To date, 33 mutations in 100 patients have been reported in the HMGCL gene. In this study 10 new mutations in 24 patients are described. They include: 5 missense mutations: c.109G>A, c.425C>T, c.521G>A, c.575T>C and c.598A>T, 2 nonsense mutations: c.242G>A and c.559G>T, one small deletion: c.853delC, and 2 mutations in intron regions: c.497+4A>G and c.750+1G>A. Two prevalent mutations were detected, 109G>T (E37X) in 38% of disease alleles analyzed and c.504_505delCT in 10% of them. Although patients are mainly of European origin (71%) and mostly Spanish (54%), the group is ethnically diverse and includes, for the first time, patients from Pakistan, Palestine and Ecuador. We also present a simple, efficient method to express the enzyme and we analyze the possible functional effects of missense mutations. The finding that all identified missense mutations cause a >95% decrease in the enzyme activity, indicates that the disease appears only in very severe genotypes."
Human Mutation 01/2009; 30(3):E520-9. · 5.69 Impact Factor
