Deleción 22q11.2 en pacientes con defecto cardiaco conotruncal y fenotipo del síndrome de la deleción 22q11.2

BACKGROUND: The 22q11.2 deletion syndrome is the most frequent human microdeletion syndrome. The phenotype is highly variable, being characterized by conotruncal heart defect, facial dysmorphisms, velopharyngeal insufficiency, learning difficulties and mental retardation. OBJECTIVE: The objective of this study was to investigate the frequency of deletion 22q11.2 in a Brazilian sample of individuals with isolated conotruncal heart defect and 22q11.2 deletion syndrome phenotype. METHODS: Twenty-nine patients were studied by classical cytogenetics, by fluorescence in situ hybridization (FISH), and by molecular techniques. RESULTS: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25% of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the clinical spectrum of the 22q11.2 deletion syndrome than in patients with isolated conotruncal heart defect. CONCLUSION: Investigating the presence of the deletion and its correlation with the patients' clinical data can help the patients and their families to have a better genetic counseling and more adequate clinical follow-up.FUNDAMENTO: El síndrome de la deleción 22q11.2 es el más frecuente síndrome de microdeleción humana. El fenotipo, altamente variable, se caracteriza por defecto cardiaco conotruncal, dismorfias faciales, insuficiencia velofaríngea, dificultad de aprendizaje y retardo mental. OBJETIVO: El objetivo de este trabajo fue investigar la frecuencia tanto de la deleción 22q11.2 en una muestra brasileña de individuos portadores de cardiopatía conotrucal aislada, como del fenotipo del síndrome de la delación 22q11.2. MÉTODOS: Se estudiaron a 29 pacientes por medio de citogenética clásica, por hibridación in situ fluorescente (FISH) y también por técnicas moleculares. RESULTADOS: El análisis citogenético por medio de bandeo G reveló cariotipo normal en todos los pacientes, con excepción de uno, que presentó cariotipo 47,XX,+idic(22)(q11.2). Con la utilización de técnicas moleculares, se observó la deleción en el 25% de los pacientes, todos portadores del fenotipo del síndrome de la deleción 22q11.2. En ningún de los casos, la deleción se heredó de los padres. La frecuencia de la deleción 22q11.2 en el grupo de pacientes portadores del espectro clínico de este síndrome resultó mayor que en el grupo de pacientes con cardiopatía conotruncal aislada. CONCLUSIÓN: La investigación de la presencia de deleción y su correlación con los datos clínicos de los pacientes pueden auxiliar los pacientes y sus familias a tener un mejor aconsejamiento genético, así como un seguimiento clínico más adecuado.FUNDAMENTO: A síndrome da deleção 22q11.2 é a mais freqüente síndrome de microdeleção humana. O fenótipo é altamente variável e caracterizado por defeito cardíaco conotruncal, dismorfias faciais, insuficiência velofaríngea, dificuldade de aprendizagem e retardo mental. OBJETIVO: O objetivo deste trabalho foi investigar a freqüência da deleção 22q11.2 em uma amostra brasileira de indivíduos portadores de cardiopatia conontrucal isolada e do fenótipo da síndrome da deleção 22q11.2. MÉTODOS: Vinte e nove pacientes foram estudados por meio de citogenética clássica, por hibridação in situ fluorescente (FISH) e por técnicas moleculares. RESULTADOS: A análise citogenética por meio de bandamento G revelou cariótipo normal em todos os pacientes, com exceção de um que apresentou cariótipo 47,XX,+idic(22)(q11.2). Com o uso de técnicas moleculares, a deleção foi observada em 25% dos pacientes, todos portadores do fenótipo da síndrome da deleção 22q11.2. Em nenhum dos casos, a deleção foi herdada dos pais. A freqüência da deleção 22q11.2 foi maior no grupo de pacientes portadores do espectro clínico da síndrome da deleção 22q11.2 do que no grupo de pacientes com cardiopatia conotruncal isolada. CONCLUSÃO: A investigação da presença da deleção e sua correlação com os dados clínicos dos pacientes podem auxiliar os pacientes e suas famílias a terem um melhor aconselhamento genético e um seguimento clínico mais adequado.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Clinical checklists in the selection of mentally retarded males for molecular screening of fragile X syndrome

Fragile X syndrome is the most frequent cause of inherited mental retardation. The phenotype in this syndrome is quite variable and less conspicuous in younger patients, making clinical diagnosis difficult and thus making molecular diagnosis necessary. The use of clinical checklists in mentally retarded individuals can help selecting patients to be given priority in the molecular investigation for the fragile-X mutation in the FMR1 gene. We evaluated two clinical checklists in a sample of 200 Brazilian male patients with mental retardation. The highest scores in the two checklists concentrated among the 19 males (9.5%) found to carry full mutations. Our results confirm the importance of fragile-X checklists as a clinical tool in the study of mentally retarded patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo Instituto de Biociências Departamento de Genética e Biologia EvolutivaUNIFESPSciEL

PRODH Polymorphisms, Cortical Volumes and Thickness in Schizophrenia

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. the study included 179 controls paired by age and gender. the samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. in summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo UNIFESP, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilFac Med ABC FMABC, Dept Ginecol & Obstet, Disciplina Genet & Reprod Humana, São Paulo, BrazilFed Univ Para, Lab Genet Humana & Med, BR-66059 Belem, Para, BrazilUniv Fed ABC, Ctr Math Computat & Cognit, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilFAPESP: 2011/50740-5FAPESP: 2007/58736-1Web of Scienc

Cytogenetic evaluation and investigation of deletion 22q11.2 in patients with structural heart defect detedted by fetal echocardiography

BV UNIFESP: Teses e dissertaçõe

Partial 5p monosomy or trisomy in 11 patients from a family with a t(5;15)(p13.3;p12) translocation

A family with six alive patients with partial monosomy 5p and five with partial trisomy 5p due to a t(5;15)(p13.3;p12) translocation is reported. the translocation was present in four generations with eight balanced carriers. This is the first molecular-cytogenetic and clinical study with both syndromes present in the same family. Using fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) probes, the breakpoint was mapped to 5p13.3, in the interval corresponding to the BAC clone RP11-1079N14, thereof resulting a 5pter-5p13.3 deletion or duplication of similar to 32 Mb. These chromosome imbalances can be considered pure, since the other imbalance produced involving chromosome 15p has no phenotypic effect. the presence of several individuals with 5p monosomy and 5p trisomy in the same family is valuable for a better delineation of both syndromes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilCtr Genet & Mol Biol, DNA Lab, Salvador, BrazilUniv Fed Bahia, Dept Pediat, Salvador, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilWeb of Scienc

Interrupção do arco aórtico tipo B em uma paciente com síndrome de olho de gato Interrupción del arco aórtico tipo B en una paciente con síndrome del ojo de gato Interrupted aortic arch type B in A patient with cat eye syndrome

Relatamos um caso de paciente com Síndrome do Olho de Gato (Cat Eye Syndrome-CES) e interrupção do arco aórtico tipo B, um achado típico na síndrome da deleção 22q11.2. A análise cromossômica e a técnica de hibridização fluorescente in situ (FISH) mostraram um cromossomo marcador isodicêntrico supranumerário com bi-satélite derivado do cromossomo 22. O segmento de 22pter a 22q11.2 no cromossomo supranumerário encontrado em nosso paciente não estava em sobreposição com a região deletada em pacientes com a síndrome da deleção 22q11.2. Entretanto, o achado de interrupção do arco aórtico tipo B não é usual na CES, mas é um defeito cardíaco freqüente na síndrome da deleção 22q11.<br>Informamos un caso de paciente con Síndrome de Ojo de Gato (Cat Eye Syndrome-CES) e Interrupción del Arco Aórtico tipo B, un hallazgo típico en el síndrome de la deleción 22q11.2. El análisis cromosómico y la técnica de hibridación in situ fluorescente (FISH) mostraron un cromosoma marcador isodicéntrico supernumerario bisatelitado derivado del cromosoma 22. El segmento de 22pter a 22q11.2 en el cromosoma supernumerario encontrado en nuestro paciente no estaba en sobreposición con la región deletada en pacientes con el síndrome de la deleción 22q11.2. Con todo, el hallazgo de interrupción del arco aórtico tipo B no es usual en el CES, sino que es un defecto cardíaco frecuente en el síndrome de deleción 22q11.<br>We report a patient with cat eye syndrome and interrupted aortic arch type B, a typical finding in the 22q11.2 deletion syndrome. Chromosomal analysis and fluorescent in situ hybridization (FISH) showed a supernumerary bisatellited isodicentric marker chromosome derived from chromosome 22. The segment from 22pter to 22q11.2 in the supernumerary chromosome found in our patient does not overlap with the region deleted in patients with the 22q11.2 deletion syndrome. However, the finding of an interrupted aortic arch type B is unusual in CES, although it is a frequent heart defect in the 22q11 deletion syndrome

Trisomy 16q21 -> qter: Seven-Year Follow-Up of a Girl With Unusually Long Survival

The 16q21 -> qter duplication is a chromosomal abnormality rarely found in liveborn infants, with only four published cases. We report here on the 7-year follow-up of a female patient with trisomy 16q21 -> qter due to a maternal balanced translocation t(4;16)(q35.2;q21). the patient shows severe mental retardation, congenital heart malformations, nephropathy, and other congenital anomalies. the derivative chromosome was characterized by GTG banding, fluorescent in situ hybridization (FISH) with different BAG probes and the array technique, in order to map the breakpoints. the patient has a 16q21 -> qter duplication, with a 4q35 -> qter monosomy, which we assume does not contribute to the abnormal phenotype. This is the first reported case of postnatal survival to the age of 7 years, an unusually long time in this chromosomal syndrome. (C) 2010 Wiley-Liss, Inc.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Bahia, Dept Gen Biol, Lab Human Genet & Mutagenesis, Salvador, BA, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, São Paulo, BrazilServac, Med Serv & Vaccinat, Salvador, BA, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, Microarrays Lab, São Paulo, BrazilUniv Fed Bahia, Dept Pediat, Salvador, BA, BrazilUniv São Paulo, Dept Pathol, LIM 03, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, Microarrays Lab, São Paulo, BrazilWeb of Scienc

Cytogenetic molecular delineation of a terminal 18q deletion suggesting neo-telomere formation

Deletion of the long arm of chromosome 18 is one of the most common segmental aneusomies compatible with life and usually involves a deletion of the terminal chromosomal region. However, the mechanisms implicated in the stabilization of terminal deletions are not well understood. In this study, we analyzed a girl with moderate mental retardation who had a cytogenetically visible terminal 18q deletion. In order to characterize the breakpoint in the terminal 18q region, we used fluorescence In situ hybridization (FISH) with bacterial artificial chromosomes (BACs) and pan-telomeric probes and also the array technique based on comparative genomic hybridization (array-CGH). FISH with pan-telomeric probes revealed no signal in the terminal region of the deleted chromosome, indicating the absence of normal telomere repeat (TTAGGG)n sequences in 18q. We suggest that neo-telomere formation by chromosome healing was involved in the repair and stabilization of this terminal deletion. (C) 2010 Elsevier Masson SAS. All rights reserved.CAPESFAPESP (Brazil