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Porto Alegre, Brazil

Tatton-Brown K.,Institute of Cancer Research | Murray A.,Institute of Cancer Research | Hanks S.,Institute of Cancer Research | Douglas J.,Institute of Cancer Research | And 29 more authors.
American Journal of Medical Genetics, Part A | Year: 2013

Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome. To date, we have identified 48 individuals with EZH2 mutations. The mutations were primarily missense mutations occurring throughout the gene, with some clustering in the SET domain (12/48). Truncating mutations were uncommon (4/48) and only identified in the final exon, after the SET domain. Through analyses of clinical data and facial photographs of EZH2 mutation-positive individuals, we have shown that the facial features can be subtle and the clinical diagnosis of Weaver syndrome is thus challenging, especially in older individuals. However, tall stature is very common, reported in >90% of affected individuals. Intellectual disability is also common, present in ~80%, but is highly variable and frequently mild. Additional clinical features which may help in stratifying individuals to EZH2 mutation testing include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry. Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. As mutation testing becomes increasingly accessible and larger numbers of EZH2 mutation-positive individuals are identified, knowledge of the clinical spectrum and prognostic implications of EZH2 mutations should improve. © 2013 Wiley Periodicals, Inc. Source

Schuck P.F.,Federal University of Rio Grande do Sul | Schuck P.F.,University of the Extreme South of Santa Catarina | Busanello E.N.B.,Federal University of Rio Grande do Sul | Moura A.P.,Federal University of Rio Grande do Sul | And 6 more authors.
Neurochemical Research | Year: 2010

High concentrations of ethylmalonic acid are found in tissues and biological fluids of patients affected by ethylmalonic encephalopathy, deficiency of short-chain acyl-CoA dehydrogenase activity and other illnesses characterized by developmental delay and neuromuscular symptoms. The pathophysiological mechanisms responsible for the brain damage in these patients are virtually unknown. Therefore, in the present work we investigated the in vitro effect of EMA on oxidative stress parameters in rat cerebral cortex. EMA significantly increased chemiluminescence and thiobarbituric acid-reactive species levels (lipoperoxidation), as well as carbonyl content and oxidation of sulfhydryl groups (protein oxidative damage) and DCFH. EMA also significantly decreased the levels of reduced glutathione (non-enzymatic antioxidant defenses). In contrast, nitrate and nitrite levels were not affected by this short organic acid. It is therefore presumed that oxidative stress may represent a pathomechanism involved in the pathophysiology of the neurologic symptoms manifested by patients affected by disorders in which EMA accumulates. © 2009 Springer Science+Business Media, LLC. Source

Martiny P.B.,Unidade de Microbiologia e Biologia Molecular | de-Paris F.,Unidade de Microbiologia e Biologia Molecular | Machado A.B.M.P.,Unidade de Microbiologia e Biologia Molecular | de Mello R.O.,Unidade de Microbiologia e Biologia Molecular | And 4 more authors.
Revista da Sociedade Brasileira de Medicina Tropical | Year: 2011

Introduction: Human cytomegalovirus (HCMV) is often reactive in latently infected immunosuppressed patients. Accordingly, HCMV remains one of the most common infections following solid organ and hemopoietic stem cell transplantations, resulting in significant morbidity, graft loss and occasional mortality. The early diagnosis of HCMV disease is important in immunosuppressed patients, since in these individuals, preemptive treatment is useful. Te objective of this study was to compare the performance of the in-house qualitative polymerase chain reaction (PCR) and pp65 antigenemia to HCMV infection in immunosuppressed patients in the Hospital de Clínicas of Porto Alegre (HCPA). Methods: A total of 216 blood samples collected between August 2006 and January 2007 were investigated. Results: Among the samples analyzed, 81 (37.5%) were HCMV-positive by PCR, while 48 (22.2%) were positive for antigenemia. Considering antigenemia as the gold standard, sensitivity, specifcity, positive predictive values and negative predictive values for PCR were 87.5%, 76.8%, 51.8% and 95.5% respectively. Conclusions: Tese results demonstrated that qualitative PCR has high sensitivity and negative predictive value (NPV). Consequently PCR is especially indicated for the initial diagnosis of HCMV infection. In the case of preemptive treatment strategy, identifcation of patients at high-risk for HCMV disease is fundamental and PCR can be useful tool. Source

de Souza L.T.,Laboratorio Of Medicina Genomica | de Souza L.T.,Federal University of Rio Grande do Sul | Kowalski T.W.,Federal University of Rio Grande do Sul | Ferrari J.,Laboratorio Of Medicina Genomica | And 9 more authors.
Oral Diseases | Year: 2016

Objectives: We investigated the association between non-syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population. Subjects and methods: Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms. Results: A total of 259 probands were analyzed. A TDT detected overtransmission of the rs2235371 G allele (P = 0.0008) in the total sample. A significant association of this allele was also observed in CLP (P = 0.0343) and CLP + CL (P = 0.0027). IRF6 haplotype analysis showed that the G/A haplotype increased the risk for cleft in children (single dose: P = 0.0038, double dose: P = 0.0022) and in mothers (single dose: P = 0.0016). The rs987525 (8q24) also exhibited an association between the A allele and the CLP + CL group (P = 0.0462). These results were confirmed in the probands with European ancestry. Conclusions: The 8q24 region plays a role in CL/P and the IRF6 G/A haplotype (rs2235371/rs642961) increases the risk for oral cleft in the Brazilian population. © 2016 John Wiley & Sons A/S. Source

Alders M.,University of Amsterdam | Al-Gazali L.,United Arab Emirates University | Cordeiro I.,Servico de Genetica | Dallapiccola B.,Ospedale Pediatrico Bambino Gesu | And 8 more authors.
Human Genetics | Year: 2014

The Hennekam lymphangiectasia–lymphedema syndrome is a genetically heterogeneous disorder. It can be caused by mutations in CCBE1 which are found in approximately 25 % of cases. We used homozygosity mapping and whole-exome sequencing in the original HS family with multiple affected individuals in whom no CCBE1 mutation had been detected, and identified a homozygous mutation in the FAT4 gene. Subsequent targeted mutation analysis of FAT4 in a cohort of 24 CCBE1 mutation-negative Hennekam syndrome patients identified homozygous or compound heterozygous mutations in four additional families. Mutations in FAT4 have been previously associated with Van Maldergem syndrome. Detailed clinical comparison between van Maldergem syndrome and Hennekam syndrome patients shows that there is a substantial overlap in phenotype, especially in facial appearance. We conclude that Hennekam syndrome can be caused by mutations in FAT4 and be allelic to Van Maldergem syndrome. © 2014, Springer-Verlag Berlin Heidelberg. Source

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