FISH studies in a girl with sporadic aniridia and an apparently balanced de novo t(11;13)(p13;q33) translocation detect a microdeletion involving the WAGR region

Conventional cytogenetic studies on a female infant with sporadic aniridia revealed what appeared to be a balanced de novo t(11;13) (p13;q33) translocation. Fluorescence in situ hybridization (FISH) investigations, however, detected the presence of a cryptic 11p13p14 deletion which included the WAGR region and involved approximately 7.5 Mb of DNA, including the PAX6 and WT1 genes. These results account for the patient's aniridia, and place her at high risk for developing Wilms' tumour. The absence of mental retardation in the patient suggests that the position of the distal breakpoint may also help to refine the mental retardation locus in the WAGR contiguous gene syndrome (Wilms', aniridia, genital anomalies and mental retardation)

Genetics And Molecular Study In Group Of Patients With Malformations Of Cerebral Cortex [estudos Genéticos E Moleculares Em Um Grande Grupo De Pacientes Com Malformações Do Córtex Cerebral]

Objectives: Malformations of cerebral cortex (MCC) are an important cause of epilepsy. Our main goals were: to search for mutations in genes responsible for MCC (FLN1, LIS1, DCX and EMX2), to map the locus for familial perisylvian polymicrogyria and to investigate the molecular mechanisms of the mutations identified. Methods: Mutation screening was performed by PCR, DHPLC and sequencing. HUMARA and Real Time PCR were performed to study the molecular mechanisms of mutations. Linkage analysis was carried out by PCR, Fragment profiler® and MLINK® software. Results: Deleterious mutations were identified in 3/108 patients. We found a G987C splicing mutation in the FLN1 in two related patients with periventricular nodular heterotopia. Skewed X-chromosome inactivation was detected as the possible mechanism responsible for clinical differences observed in the two patients. An A1385C transversion (H277P) in LIS1 was identified in one patient with lisencephaly. Only neutral variants were identified in DCX and EMX2. Linkage analysis has detected a locus in Xq27.2-Xq27.3 for familial polymicrogyria. Conclusion: We believe that the low frequency of mutations identified may be due to mosaicism, mutations in non-coding regions, deletions and patients with atypical neuroimaging findings. Deleterious mutations in EMX2 were not found in patients with schizencephaly and polymicrogyria. We found a locus for familial perisylvian polymicrogyria in Xq27.2-Xq27.3.143101105Brunelli, S., Faiella, A., Capra, V., Nigro, V., Simeone, A., Cama, A., Germline mutation in the homeobox gene EMX2 in patients with severe schizenchephaly (1996) Nature Genet, 12, pp. 94-96Des Portes, V., Francis, F., Pinard, J.-M., Desguerre, I., Moutard, M.-L., Snoeck, I., Meiners, L.C., Beldjord, C., Doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH) (1998) Human Molecular Genetics, 7 (7), pp. 1063-1070. , DOI 10.1093/hmg/7.7.1063Dobyns, W.B., Truwit, C.L., Ross, M.E., Matsumoto, N., Pilz, D.T., Ledbetter, D.H., Gleeson, J.G., Barkovich, A.J., Differences in the gyral pattern distinguish chromosome 17-linked and X- Linked lissencephaly (1999) Neurology, 53 (2), pp. 270-277Fox, J.W., Lamperti, E.D., Eksioglu, Y.Z., Hong, S.E., Feng, Y., Graham, D.A., Scheffer, I.E., Walsh, C.A., Mutations in filamin 1 prevent migration of cerebral cortical neurons in human Periventricular heterotopia (1998) Neuron, 21 (6), pp. 1315-1325. , DOI 10.1016/S0896-6273(00)80651-0Grantham, R., Amino acid difference formula to help protein evolution (1974) Science, 185, pp. 862-864Kruglyak, L., Daly, M.J., Reeve-Daly, M.P., Lander, E.S., Parametric and nonparametric linkage analysis: A unified multipoint approach (1996) American Journal of Human Genetics, 58 (6), pp. 1347-1363Kuzniecky, R., Murro, A., King, D., Morawetz, R., Smith, J., Powers, R., Yaghmai, F., Snead, O.C., Magnetic resonance imaging in childhood intractable partial epilepsies: Pathologic correlations (1993) Neurology, 43 (4 I), pp. 681-687Leventer, R.J., Cardoso, C., Ledbetter, D.H., Dobyns, W.B., LIS1 missense mutations cause milder lissencephaly phenotypes including a child with normal IQ (2001) Neurology, 57, pp. 416-422Palmini, A., Andermann, E., Andermann, F., Prenatal events and genetic factors in epileptic patients with neuronal migration disorders (1994) Epilepsia, 35 (5), pp. 965-973. , DOI 10.1111/j.1528-1157.1994.tb02541.xParrini, E., Ramazzotti, A., Dobyns, W.B., Mei, D., Moro, F., Veggiotti, P., Marini, C., Guerrini, R., Periventricular heterotopia: Phenotypic heterogeneity and correlation with Filamin a mutations (2006) Brain, 129 (7), pp. 1892-1906. , DOI 10.1093/brain/awl125Reiner, O., Carrozzo, R., Shen, Y., Wehnert, M., Faustinella, F., Dobyns, W.B., Caskey, C.T., Ledbetter, D.H., Isolation of a Miller-Dieker lissencephaly gene containing G protein beta- Subunit-like repeats (1993) Nature, 364 (6439), pp. 717-721. , DOI 10.1038/364717a0Robertson, S.P., Twigg, S.R.F., Sutherland-Smith, A.J., Biancalana, V., Gorlin, R.J., Horn, D., Kenwrick, S.J., Wilkie, O.M., Localized mutations in the gene encoding the cytoskeletal protein filamin a cause diverse malformations in humans (2003) Nature Genetics, 33 (4), pp. 487-491. , DOI 10.1038/ng1119Santos, N.F., Secolin, R., Brandao-Almeida, I.L., Silva, M.S., Torres, F.R., Tsuneda, S.S., Guimaraes, C.A., Lopes-Cendes, I., A new candidate locus for bilateral perisylvian polymicrogyria mapped on chromosome Xq27 (2008) American Journal of Medical Genetics, Part a, 146 (9), pp. 1151-1157. , DOI 10.1002/ajmg.a.32270Terwillinger, J.D., Ott, J., (1993) Handbook of Human Genetic Linkage, , Maryland: Johns HopkinsTietjen, I., Bodell, A., Apse, K., Mendonza, A.M., Chang, B.S., Shaw, G.M., Comprehensive EMX2 genotyping of a large schizencephaly case series (2007) Am J Med Genet a, 143, pp. 1313-1316Torres, F.R., Montenegro, M.A., Marques-De-Faria, A.P., Guerreiro, M.M., Cendes, F., Lopes-Cendes, I., Mutation screening in a cohort of patients with lissencephaly and subcortical band heterotopia (2004) Neurology, 62 (5), pp. 799-802Tsuneda, S.S., Torres, F.R., Montenegro, M.A., Guerreiro, M.M., Cendes, F., Lopes-Cendes, I., A new missense mutation found in the FLN1 gene in a family with Bilateral Periventricular Nodular Heterotopia (BPNH) alters the splicing process (2007) J Mol Neurosci, 35, pp. 195-200Uyanik, G., Morris-Rosendahl, D.J., Stiegler, J., Klapecki, J., Gross, C., Berman, Y., Location and type of mutation in the LIS1 gene do not predict phenotypic severity (2007) Neurology, 69, pp. 442-447Villard, L., Nguyen, K., Cardoso, C., Martin, C.L., Weiss, A.M., Sifry-Platt, M., Grix, A.W., Dobyns, W.B., A locus for bilateral perisylvian polymicrogyria maps to Xq28 (2002) American Journal of Human Genetics, 70 (4), pp. 1003-1008. , DOI 10.1086/339433Wyllie, E., Comair, Y., Ruggieri, P., Raja, S., Prayson, R., Epilepsy surgery in the setting of periventricular leukomalacia and focal cortical dysplasia (1996) Neurology, 46 (3), pp. 839-84

Eumicetoma de grãos pretos por Madurella grisea: registro de dois casos Eumycotic mycetoma of black grains caused by Madurella grisea: report of two cases

Os Autores registram dois casos de eumicetoma de grãos pretos, com localização podal, procedentes da Bahia, provocados por Madurella grisea Mackinnon et al., 1949. São estudadas a estrutura dos grãos, bem como as características micromorfológicas do fungo em vida saprofítica. Acreditam os Autores que estas observações correspondem ao sétimo e oitavo casos registrados na literatura do país, provocadas por este fungo. Os Autores consideram nomen dubium ou nomina confusa as seguintes espécies de Madurella: M. ramiroi, M. oswaldoi, M. bovoi, M. tozeuri, M. mansonii, M. brumpti, M. reynieri, M. americana, M. lackawanna e M. ikedae, o mesmo ocorrendo com a chamada Rubromadurella mycetomi. As únicas espécies válidas são Madurella mycetomatis McGinnis, 1980 (=Madurella mycetomi Brumpt, 1905) e Madurella grisea Mackinnon et al., 1949. Nos dois casos registrados o tratamento com itraconazol, por um período de 3 meses não fez regredir as lesões, havendo ligeira melhora clínica.<br>Two cases of black grains eumycotic mycetoma, occurring on a foot, are reported. Both proceeded from the State of Bahia (Brazil), and in both the etiologic agent was Madurella grisea Mackinnon et al., 1949. The grains structure as well as the micromorphologic characteristics of the fungus in saprophytic life were studied. It is the Author's belief that these observations correspond to the 7th and 8th cases reported in the Brazilian medical literature. The Authors do consider the following Madurella species as nomen dubium or nomina confusa: M. ramiroi, M. oswaldoi, M. bovoi, M. tozeuri, M. mansonii, M. brumpti, M. reynieri, M. americana, M. lackawanna e M. ikedae and the same for Rubromadurella mycetomi. The only valid species must be Madurella mycetomatis McGinnis, 1980 (=Madurella mycetomi Brumpt, 1905) and Madurella grisea Mackinnon et al., 1949. Treatment with itraconazole in both reported cases, for a 3 month duration, did not produce any regression of the lesions, the clinical improvement being meager