Decio Brunoni

Universidade Federal de São Paulo, San Paulo, São Paulo, Brazil

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Publications (68)152.5 Total impact

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    ABSTRACT: We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpoints—unique for each patient—could be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 07/2014; 164(7). DOI:10.1002/ajmg.a.36512 · 2.05 Impact Factor
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    ABSTRACT: Van den Ende-Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553-559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2010] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 05/2014; 164(5). DOI:10.1002/ajmg.a.36425 · 2.05 Impact Factor
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    ABSTRACT: Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. In the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. We used data from a factorial trial that evaluated the efficacy of tDCS and sertraline and enrolled 120 moderate-to-severe, antidepressant-free participants. In the present study, we used analyses of variance to evaluate whether the BDNF (Val/Val vs. Met-carries) and 5-HTTLPR alleles (long/long vs short-carriers) were predictors of tDCS (active/sham) and sertraline (sertraline/placebo) response. Analyses were conducted on the polymorphisms separately and also on their interaction. Genotype frequencies were in Hardy-Weinberg equilibrium. BDNF polymorphism was not associated with treatment response. We found that 5-HTTLPR predicted tDCS effects as long/long homozygotes displayed a larger improvement comparing active vs. sham tDCS, while short-allele carriers did not. A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS "top-down" antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2013; 23(11). DOI:10.1016/j.euroneuro.2013.03.009 · 5.40 Impact Factor
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    ABSTRACT: Ring chromosome 15 is a rare disorder, with only a few over 40 cases reported in the literature. There are only two previous reports of cases where patients with ring chromosome 15 have been followed-up. We report here on the 20-year clinical and cytogenetic follow-up of a patient with a ring chromosome 15. Our patient, a Caucasoid Asian woman, presented with short stature, microcephaly, minor dysmorphic features, hyperextensible knees, generalized hirsutism, café-au-lait and small hypochromic spots spread over her face and the front of her chest and abdomen, dorsolumbar scoliosis and mild intellectual disability. She was followed-up from the age of eight to 28 years. When she was 27 years old, she was reported by her mother to present with compulsive overeating and an aggressive mood when challenged. Karyotyping revealed that the majority of her cells harbored one normal chromosome and one ring chromosome. Silver staining revealed the presence of the nucleolar organizer region in the ring chromosome. Ring loss and/or secondary aberrations exhibited a slight increase over time, from 4.67% in 1989 to 7.67% in 2009, with the presence of two monocentric rings, cells with interlocked rings, a dicentric ring, and broken or open rings. A genome-wide array technique detected a 5.5Mb deletion in 15q26.2. We observed that some phenotypic alterations in our patient can be associated with gene loss and haploinsufficiency. Other features may be related to different factors, including ring instability and epigenetic factors.
    Journal of Medical Case Reports 09/2012; 6(1):283. DOI:10.1186/1752-1947-6-283
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    ABSTRACT: We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling.
    Gene 03/2012; 496(1):59-62. DOI:10.1016/j.gene.2012.01.007 · 2.08 Impact Factor
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    ABSTRACT: Pervasive developmental disorders (PDD) are characterized by comprehensive and qualitative abnormalities affecting three areas of development: reciprocal social interaction, communication, and a repetitive, stereotyped behavioral repertoire, of limited interests. Genetic studies have identified the recurrence of PDD in the same family. The present study aimed to trace the occurrence of signs and symptoms of PDD in the siblings of patients with this diagnosis. The study included 25 subjects from 19 families. Data collection was performed using the Brazilian version of the Autism Screening Questionnaire (ASQ). Two cases of PDD in siblings were confirmed (10.52% of cases): a monozygotic twin brother and the brother of a proband with a diagnosis of Asperger syndrome. Our data indicate higher rates of PDD in siblings than described in the literature (2-6%), close to the findings that suggest a 10% rate of familial recurrence in dizygotic twins. This result provides evidence of possible neurogenetic factors to explain the occurrence of PDD in relatives of the probands assessed and underscores the need to screen not only the child under evaluation, but also their siblings.Keywords: Siblings, genetics, autism spectrum disorders.
    Revista de Psiquiatria do Rio Grande do Sul 12/2010; 33(2):116-120. DOI:10.1590/S0101-81082011000200009
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    ABSTRACT: We present a 20-year follow-up on a patient with a ring chromosome 14. The ring chromosome was studied by fluorescence in-situ hybridization (FISH), multiplex-ligation probe amplification (MLPA), and genome wide SNP array, and no deletions of chromosome 14 were detected, although the telomeric repeat sequence was absent from the ring chromosome. The patient had skeletal abnormalities, and susceptibility to infections, as well as seizures and retinal pigmentation, which are commonly found in individuals with a ring 14. Our patient corroborates the idea that even when no genes are lost during ring formation, a complete ring chromosome can produce phenotypic alterations, which presumably result from ring instability or gene silencing due to the new chromosomal architecture.
    American Journal of Medical Genetics Part A 11/2010; 152A(11):2865-9. DOI:10.1002/ajmg.a.33689 · 2.05 Impact Factor
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    ABSTRACT: The most prevalent type of structural variation in the human genome is represented by copy number variations that can affect transcription levels, sequence, structure and function of genes. In the present study, we used the multiplex ligation-dependent probe amplification (MLPA) technique and quantitative PCR for the detection of copy number variation in 132 intellectually disabled male patients with normal karyotypes and negative fragile-X-testing. Ten of these patients (7.6%) showed copy number variation in the subtelomeric regions, including deletions and duplications. Duplications of the SECTM1 gene, located at 17q25.3, and of the FLJ22115 gene, located at 20p13, could be associated with phenotype alterations. This study highlights the relevance in the aetiology of intellectual disability of subtelomeric rearrangements that can be screened by MLPA and other molecular techniques.
    Journal of Intellectual Disability Research 10/2010; 54(10):938-42. DOI:10.1111/j.1365-2788.2010.01325.x · 2.41 Impact Factor
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    ABSTRACT: The aim of this study was to improve the completion of item 34 on birth certificates at four maternity hospitals in the city of São Paulo, Brazil, in the year 2008. The database of the Municipal Health Department's Information System on Live Births was used to monitor trends in reporting birth defects. An electronic web-based medical record was used to refer indeterminate cases to a leading medical genetics referral center. The electronic medical record contained the patient history, physical examination, and photographs of the newborn. Four maternity hospitals were assessed, with a total of 10,000 births during the year. None of the four hospitals had a staff geneticist. According to the Information System on Live Births, there was an increase in the number of birth defects reported by the four maternity hospitals when compared to previous years and to records for the city of São Paulo as a whole. Based on the findings, the web-based referral and counter-referral method proved efficient.
    Cadernos de saúde pública / Ministério da Saúde, Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública 07/2010; 26(7):1383-90. · 0.89 Impact Factor
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    ABSTRACT: The Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8) or atypical HOS (1), isolated congenital heart defects (16) or isolated upper-limb malformations (7). Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T) in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7) was detected in a patient with isolated heart malformations and also in his clinically normal father.
    Genetics and Molecular Biology 04/2010; 33(2):232-6. DOI:10.1590/S1415-47572010005000051 · 0.88 Impact Factor
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    ABSTRACT: OBJECTIVE: To identify the main characteristics of the behavioral phenotype of children and adolescents with Prader-Willi syndrome. METHODS: Eleven children and adolescents with clinical and cytogenetic-molecular diagnosis of Prader-Willi syndrome were studied. Data collection was obtained by the Child Behavior Checklist for Ages 6-18 (CBCL/6-18). Bivariate correlations were used to test the association between the analyzed variables, being significant p<0.05. RESULTS: The behavioral profile obtained was considered as clinical in different scales of the CBCL/6-18 tool. A behavioral pattern with high frequency of aggression, rule breaking and opposition was observed. Statistically significant correlations between attention and social problems and between thought problems and breaking rules were identified. CONCLUSIONS: The studied patients represent a group of psychiatric risk, with behavioral changes that, in the long-term, can lead to mood disorders, attention deficit hyperactivity disorder and oppositional defiant behavior, among other disorders.
    Revista Paulista de Pediatria 03/2010; 28(1):63-69. DOI:10.1590/S0103-05822010000100011
  • Cadernos de Saúde Pública 01/2010; 26(7). DOI:10.1590/S0102-311X2010000700017 · 0.89 Impact Factor
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    ABSTRACT: Ring chromosomes are often associated with abnormal phenotypes due to loss of genomic material and also because of ring instability at mitosis after sister chromatid exchange events. We investigated ring chromosome instability in six patients with ring chromosomes 4, 14, 15, and 18 by examining 48- and 72-h lymphocyte cultures at the first, second and subsequent cell divisions after bromodeoxyuridine incorporation. Although most cells from all patients showed only one monocentric ring chromosome, ring chromosome loss and secondary aberrations were observed both in 48- and 72-h lymphocyte cultures and in metaphase cells of the different cell generations. We found no clear-cut correlation between ring size and ring instability; we also did not find differences between apparently complete rings and rings with genetic material loss. The cytogenetic findings revealed secondary aberrations in all ring chromosome patients. We concluded that cells with ring chromosome instability can multiply and survive in vivo, and that they can influence the patient's phenotype.
    Genetics and molecular research: GMR 01/2010; 9(1):134-43. DOI:10.4238/vol9-1gmr707 · 0.85 Impact Factor
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    ABSTRACT: Fetuses exposed to aminopterin during the 8th-9th week of development may show aminopterin embryophathy (AE). Surviving children have a specific phenotype that includes unusual face, skull, and skeletal abnormalities. Fraser et al. [Fraser et al. (1987); Clin Genet 32:28-34] described two children with multiple malformations characteristic of the aminopterin syndrome but without history of exposure to aminopterin in the mothers and suggested that this represents a new syndrome, the aminopterin syndrome-like sine aminopterin (ASSA) syndrome. Here we describe a 9-year-old girl, born to unaffected first cousin parents. She has short stature, microcephaly, broad forehead with high hair implantation; sparse and fine hair, areas of alopecia; arched eyebrows with upturned hair, synophris; ocular hypertelorism, epicanthal folds, palpebral ptosis; oligodontia; low-set and small ears with hypoplasia of antihelices; brachydactyly, clinodactyly of both 4th and 5th fingers; hypoplasia of the 4th metacarpal and clinodactyly of the 4th and 5th toes; overlap of the second over the third toe; bilateral hip luxation; patent foramen ovale; left posterior diaphragmatic hernia, absence of spleen and horseshoe kidney. She, her mother and her brother have a karyotype of 46,XX, with an inv(9)(p12q13) polymorphism. Although this patient has some characteristics did not described before in patients with ASSA such as, palpebral ptosis, oligodontia, left posterior diaphragmatic hernia, absence of spleen, and horseshoe kidney, her phenotype strongly suggest she has the pseudoaminopterin syndrome. However, we do not exclude the possibility that this is a different condition not described previously.
    American Journal of Medical Genetics Part A 12/2009; 149A(12):2843-8. DOI:10.1002/ajmg.a.33125 · 2.05 Impact Factor
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    ABSTRACT: Rett syndrome (RS) is a severe neurodevelopmental X-linked dominant disorder caused by mutations in the MECP2 gene. To search for point mutations on the MECP2 gene and to establish a correlation between the main point mutations found and the phenotype. Clinical evaluation of 105 patients, following a standard protocol. Detection of point mutations on the MECP2 gene was performed on peripheral blood DNA by sequencing the coding region of the gene. Classical RS was seen in 68% of the patients. Pathogenic point mutations were found in 64.1% of all patients and in 70.42% of those with the classical phenotype. Four new sequence variations were found, and their nature suggests patogenicity. Genotype-phenotype correlations were performed. Detailed clinical descriptions and identification of the underlying genetic alterations of this Brazilian RS population add to our knowledge of genotype/phenotype correlations, guiding the implementation of mutation searching programs.
    Arquivos de neuro-psiquiatria 10/2009; 67(3A):577-84. DOI:10.1590/S0004-282X2009000400001 · 1.01 Impact Factor
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    ABSTRACT: Patients with fragile X syndrome present a variable phenotype, which contributes to the underdiagnosing of this condition. The use of clinical checklists in individuals with intellectual disability can help in selecting patients to be given priority in the molecular investigation of the fragile X mutation in the FMR1 gene. Some features included in checklists are better predictors than others, but they can vary among different populations and with patient age. In the present study, we evaluated 20 features listed in four clinical checklists from the literature, using a sample of 192 Brazilian male patients presenting with intellectual disability (30 positive and 162 negative for fragile X mutation). After statistical analysis, 12 out of the 20 items analyzed showed significant differences in their distributions between the two groups. These features were grouped in a new checklist that can help clinicians in their referral for fragile X testing in patients with developmental delay.
    Journal of Intellectual Disabilities 09/2009; 13(3):239-48. DOI:10.1177/1744629509348429
  • Journal of child neurology 06/2009; 24(5):642-3. DOI:10.1177/0883073808322339 · 1.67 Impact Factor
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    ABSTRACT: Background: The Pervasive Developmental Disorders (PDD) includes a broad spectrum of disorders of development characterized by the presence of disturbances in social skills, in communication and behavior, with restricted and repetitive interests. Diagnose correctly the PDD and conduct research in this area is very important for the knowledge of professionals who work in the area and interventions ever earlier. Objectives: Describing the group of research and evaluation on PDD of the Post-Graduate Program of Developmental Disorders, Center for Biological Sciences and Health, Mackenzie Presbyterian University, São Paulo, Brazil. Methods: Description of the protocol of evaluation and analysis of the database group's evaluation of PDD. Results: The evaluation: anamnesis, screening questionnaires (SCQ: Social Screening questionnaire, ABC: Autism Behavior Checklist), neuropsychological assessment (WISC III, PEP-R, Trail Making Test, Wisconsin test, Rey) evaluation speech with an emphasis on language and social cognition (Pragmatic, Language Competences, Symbolic Maturity, Shared Attention, Empathy Card-deck, card-deck of basic facial expression in photos and drawings, Theory of Mind tasks, Social Stories Questionnaire), physical examination, neurological examination, assessment by equipment that records the eye movement (Tobii eye tracking) and implementation of protocols for scientific research. At the end of each assessment, the group concludes a diagnosis. Then it is done with a report of conduct and guidelines, which are explained in a meeting with the family of the individual assessed. From 2007 until 2008 were assessed 38 subjects, with 30 subjects were male and 8 female, aged between 2 and 39 years, with the largest concentration 5 to 11 years. Diagnostics: 8 subjects did not meet criteria for PDD, 8 received a diagnosis of PDD, 7 of autism, 6 of Asperger Syndrome, 8 of Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), and 1 with a semantic pragmatic disorder. Conclusions: The group described conducts research and evaluations, reiterating the importance of the development of knowledge in the area, suitable for early intervention.
    International Meeting for Autism Research 2009; 05/2009
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    04/2009; 34(1). DOI:10.7322/abcs.v34i1.141
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    ABSTRACT: To translate into Portuguese, back-translate, culturally adapt and validate a screening instrument for pervasive developmental disorder, the Autism Screening Questionnaire, for use in Brazil. A sample of 120 patients was selected based on three groups of 40: patients with a clinical diagnosis of pervasive developmental disorder, Down syndrome, or other psychiatric disorders. The self-administered questionnaire was applied to the patients' legal guardians. Psychometric measures of the final version of the translated questionnaire were tested. The score of 15 had sensitivity of 92.5% and specificity of 95.5% as a cut-off point for the diagnosis of pervasive developmental disorder. Internal validity for a total of 40 questions was 0.895 for alpha and 0.896 for KR-20, ranging from 0.6 to 0.8 for both coefficients. Test and retest reliability values showed strong agreement for most questions. The final version of this instrument, translated into Portuguese and adapted to the Brazilian culture, had satisfactory measurement properties, suggesting preliminary validation proprieties. It was an easy-to-apply, useful tool for the diagnostic screening of individuals with pervasive developmental disorder.
    Revista Brasileira de Psiquiatria 04/2009; 31(1):30-3. DOI:10.1590/S1516-44462009000100008 · 1.64 Impact Factor

Publication Stats

1k Citations
152.50 Total Impact Points

Institutions

  • 1998–2014
    • Universidade Federal de São Paulo
      • • Departamento de Morfologia e Genética
      • • Departamento de Medicina
      • • Departamento de Patologia
      • • Departamento de Ortopedia e Traumatologia
      • • Departamento de Dermatologia
      San Paulo, São Paulo, Brazil
  • 2010
    • University of São Paulo
      San Paulo, São Paulo, Brazil
  • 2009–2010
    • Universidade Presbiteriana Mackenzie
      San Paulo, São Paulo, Brazil
    • Universidade de Santo Amaro
      San Paulo, São Paulo, Brazil
  • 2007
    • CEP America
      Emeryville, California, United States