CLINICAL, NEUROIMAGING AND CYTOGENETIC FINDINGS IN 20 PATIENTS WITH CORPUS CALLOSUM DYSGENESIS

ABSTRACT -Twenty children with corpus callosum agenesis or hypoplasia were evaluated under a standardized investigation protocol. Psychomotor retardation, seizures, and craniofacial anomalies were the most prominent findings. There were three cases of chromosomal anomalies, all of them representing trisomy of chromosome 8. KEY WORDS: corpus callosum agenesis, chromosomal anomaly, trisomy 8. Achados clínicos, citogenéticos e de neuroimagem em 20 pacientes com disgenesia do corpo caloso Achados clínicos, citogenéticos e de neuroimagem em 20 pacientes com disgenesia do corpo caloso Achados clínicos, citogenéticos e de neuroimagem em 20 pacientes com disgenesia do corpo caloso Achados clínicos, citogenéticos e de neuroimagem em 20 pacientes com disgenesia do corpo caloso Achados clínicos, citogenéticos e de neuroimagem em 20 pacientes com disgenesia do corpo caloso RESUMO -Vinte pacientes com disgenesia do corpo caloso foram avaliados através de um protocolo padronizado. Retardo neuropsicomotor, convulsões e dismorfias faciais foram os achados mais proeminentes. Três casos de anomalia cromossômica foram observados, todos representados por trissomia do cromossomo 8. PALAVRAS-CHAVE: disgenesia do corpo caloso, anomalia cromossômica, trissomia 8

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio

Familial Myelodysplastic/Acute Leukemia Syndromes—Myeloid Neoplasms with Germline Predisposition

Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text

Clinical, neuroimaging and cytogenetic findings in 20 patients with corpus callosum dysgenesis Achados clínicos, citogenéticos e de neuroimagem em 20 pacientes com disgenesia do corpo caloso

Twenty children with corpus callosum agenesis or hypoplasia were evaluated under a standardized investigation protocol. Psychomotor retardation, seizures, and craniofacial anomalies were the most prominent findings. There were three cases of chromosomal anomalies, all of them representing trisomy of chromosome 8.<br>Vinte pacientes com disgenesia do corpo caloso foram avaliados através de um protocolo padronizado. Retardo neuropsicomotor, convulsões e dismorfias faciais foram os achados mais proeminentes. Três casos de anomalia cromossômica foram observados, todos representados por trissomia do cromossomo 8

Screening and characterization of BRCA2 c.156_157insAlu in Brazil: Results from 1380 individuals from the South and Southeast

Accepted manuscriptPortuguese immigration to Brazil occurred in several waves and greatly contributed to the genetic composition of current Brazilian population. In this study, we evaluated the frequency of a Portuguese founder Alu insertion in BRCA2 exon 3 (c.156_157insAlu) among individuals fulfilling Hereditary Breast and Ovarian Cancer (HBOC) syndrome criteria in 1,380 unrelated families originated from three distinct Brazilian States. We identified the c.156_157insAlu BRCA2 mutation in nine (9/1,380; 0.65%) probands analised. In carrier probands, European ancestry had the highest proportion (80%), followed by the African (10%) and Amerindian and in most families with the rearrangement, haplotype analyses were compatible with the Portuguese ancestral haplotype. In conclusion, the present study reports a low albeit relevant frequency of the Portuguese BRCA2 founder mutation c.156_157insAlu in Brazilian patients at-risk for HBOC Brazilian population.CNPq (408313/2016-1), FAPERGS (PRONEX: 16/2551-0000486-2), Hospital de Clínicas de Porto Alegre (FIPE-HCPA), FINEP-CT-INFRA (02/2010) and FAPESP (2013/24633-2). RMR, EIP and PA-P are recipients of National Council of Technological and Scientific Development (CNPq) scholarshipsinfo:eu-repo/semantics/publishedVersio