UBM - Unidade de Biologia Molecular
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- Two pairs of proven monozygotic twins discordant for familial amyloid neuropathy (FAP) TTR Met 30.Publication . MUNAR‐QUES, M.; PEDROSA, J.L.; COELHO, T.; GUSMAO, L.; SERUCA, R.; AMORIM, A.; SEQUEIROS, J.J Med Genet. 1999 Aug;36(8):629-32. Two pairs of proven monozygotic twins discordant for familial amyloid neuropathy (FAP) TTR Met 30. Munar-Qués M, Pedrosa JL, Coelho T, Gusmão L, Seruca R, Amorim A, Sequeiros J. Grupo de Estudio de la PAF, Palma de Mallorca, Spain. Abstract Twin studies are an important tool in medical genetics for the evaluation of the relative roles of genetic and non-genetic factors in several diseases. Familial amyloidotic polyneuropathy type I (FAP-I), TTR Met 30, was present in two sets of proven monozygotic (MZ) twins, one from Majorca and the other from Portugal. Monozygosity was established by analysis of DNA polymorphisms. Both pairs were discordant for age at onset and some clinical manifestations of FAP-I. We reviewed the differences in age at onset and clinical features in both sets and in two other pairs of presumed MZ twins with FAP-I and compared them with those in MZ twin pairs with other Mendelian disorders, such as neurofibromatosis type 1, Huntington's disease, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. We conclude that, in addition to the postulated modifying genes, there must be a significant contribution from non-genetic factors to the phenotypic variability of FAP-I (age at onset and clinical expression), either because of environmental differences or stochastic events during (or after) the twinning process. PMID: 10465115 [PubMed - indexed for MEDLINE]PMCID: PMC1762972
- Homozygosity mapping of a third Joubert syndrome locus to 6q23.Publication . Lagier-Tourenne, C.; Boltshauser, E.; Breivik, N.; Gribaa, M.; Bétard, C.; Barbot, C.; Koenig, M.J Med Genet. 2004 Apr;41(4):273-7. Homozygosity mapping of a third Joubert syndrome locus to 6q23. Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Bétard C, Barbot C, Koenig M. IGBMC, CNRS/INSERM/ULP, Illkirch, C.U. de Strasbourg, France. Abstract BACKGROUND: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign") and suggestive facial features. JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys. JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases. METHODS: A large consanguineous Joubert family (five affected) was analysed for linkage with a marker set covering the entire genome and 16 smaller families were subsequently tested for candidate loci. RESULTS: We report here the identification of a third locus in 6q23 (JBTS3) from the study of two consanguineous families. LOD score calculation, including the consanguinity loops, gave a maximum value of 4.1 and 2.3 at q = 0 for the two families, respectively. CONCLUSIONS: Linkage between the disease and the D6S1620-D6S1699 haplotype spanning a 13.1 cM interval is demonstrated. Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction. PMID: 15060101 [PubMed - indexed for MEDLINE]PMCID: PMC1735723
- Identification of a new mtDNA mutation (14724G>A) associated with mitochondrial leukoencephalopathyPublication . PEREIRA, C.; NOGUEIRA, C.; BARBOT, C.; TESSA, A.; SOARES, C.; FATTORI, F.; GUIMARÃES, A.; SANTORELLI, F.M.; VILARINHO, L.Biochem Biophys Res Commun. 2007 Mar 23;354(4):937-41. Epub 2007 Jan 23. Identification of a new mtDNA mutation (14724G>A) associated with mitochondrial leukoencephalopathy. Pereira C, Nogueira C, Barbot C, Tessa A, Soares C, Fattori F, Guimarães A, Santorelli FM, Vilarinho L. Instituto de Genética Médica Jacinto de Magalhães, Praça Pedro Nunes, 88, 4099-028 Porto, Portugal. Abstract We report a novel 14724G>A mutation in the mitochondrial tRNA glutamic acid gene in a 4-year-old boy with myopathy and leukoencephalopathy. A muscle biopsy showed cytochrome c oxidase-negative ragged-red fibers and biochemical analysis of the respiratory chain enzymes in muscle homogenate revealed partial complex I and complex IV deficiencies. The mutation, which affects the dihydrouridine arm at a conserved site, was nearly homoplasmic in muscle and heteroplasmic in blood DNA of the proband, but it was absent in peripheral leukocytes from the asymptomatic mother, sister, and two maternal aunts, suggesting that it arose de novo. This report proposes to look for variants in the mitochondrial genome when dealing with otherwise undetermined leukodystrophies of childhood. PMID: 17266923 [PubMed - indexed for MEDLINE]
- Changes in the Clonal Nature and Antibiotic Resistance Profiles of Methicillin-Resistant Staphylococcus aureus Isolates Associated with Spread of the EMRSA-15 Clone in a Tertiary Care Portuguese HospitalPublication . Amorim, M.; Faria, N.; Oliveira, D.; Vasconcelos, C.; Cabeda, J.; Mendes, A.; Calado, E.; Castro, A.; Ramos, M.; Amorim, J.; Lencastre, H.Abstract Two hundred eighty methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates recovered from a tertiary care hospital in Oporto, Portugal, between 2003 and 2005 were studied by a combination of molecular typing techniques in order to investigate the genetic backgrounds associated with the changes in the resistance phenotypes observed since 2001 and compare them to those previously found in the hospital. All MRSA isolates were grouped into resistance profiles for a panel of seven antibiotics and characterized by pulsed-field gel electrophoresis (PFGE) and SCCmec (staphylococcal cassette chromosome mec) typing. Representative isolates of PFGE types were further studied by spa typing and multilocus sequence typing. Our findings clearly document that the increasing isolation of nonmultiresistant MRSA strains was associated with the decline (from 69% in 1996 to 2000 to 12% in 2003 to 2005) and massive replacement of the multiresistant Brazilian clone (ST239-IIIA) by the epidemic EMRSA-15 clone (ST22-IV), in which resistance to antibiotics other than beta-lactams is very rare, as the major clone (80% of isolates). The Iberian clone (ST247-IA), a major clone in 1992 to 1993, was represented in the present study by just one isolate. Two other pandemic MRSA clones were detected, as sporadic isolates, for the first time in our hospital: the New York/Japan (ST5-II) and the EMRSA-16 (ST36-II) clones. Furthermore, the pattern of susceptibility of MRSA isolates both to gentamicin and to trimethoprim-sulfamethoxazole was shown to be an excellent phenotypic marker for the discrimination of the EMRSA-15 clone from other nonmultiresistant MRSA clones present in our hospital.