Três rearranjos diferentes, três fenótipos diferentes :Estudo Familiar Cromossoma 14

Introdução – Cromossomas derivativos são o resultado de rearranjos estruturais que tanto podem ocorrer num só, como entre dois ou mais cromossomas. Estes rearranjos dão origem a cromossomas estruturalmente anormais, podendo resultar um fenótipo normal ou mais ou menos grave, dependendo do tipo de anomalia encontrada. Materiais e métodos – Caso índex: homem de 55 anos, referenciado para estudos de citogenética clássica (cariótipo com bandas GTG de alta resolução) e molecular (MLPA – kits P036 e P070 e FISH com sonda subtelomérica especifica para o cromossoma 14) por apresentar um quadro clínico de atraso mental. Posteriormente realizaram-se estudos citogenéticos a uma irmã com atraso cognitivo e baixa estatura, e a mais quatro familiares com fenótipos normais. Resultados – O cariótipo do caso índex revelou a existência de uma anomalia cromossómica estrutural desequilibrada num dos cromossomas 14, sugerindo uma deleção da banda 14q32, e uma duplicação do braço curto localizada na parte terminal do braço longo. Nos estudos de citogenética molecular, a técnica de MLPA identificou uma deleção da região subtelomérica no braço longo do cromossoma 14, em ambos os kits e, posteriormente, a técnica de FISH comprovou essa deleção. Após estudos familiares, concluiu-se que dois dos irmãos apresentavam anomalias cromossómicas distintas do caso índex, envolvendo igualmente o cromossoma 14. Apesar de não ser possível efetuar o cariótipo à mãe (falecida), presume-se que estas alterações tenham tido origem numa anomalia cromossómica materna, uma vez que o pai deste indivíduo apresentava um cariótipo normal. Conclusões – Os autores apresentam os resultados citogenéticos dos vários indivíduos estudados, e realçam a raridade da existência de três rearranjos diferentes (um deles aparentemente equilibrado e dois desequilibrados), envolvendo o cromossoma 14, encontrados numa mesma família

Large interstitial del(13)(q13q14.3): the importance of detailed clinical information in cytogenetic studies

Interstitial deletions of chromosome 13 are known to be associated with retinoblastoma. A wider syndrome may accompany the deletion, including mental retardation and craniofacial dysmorphism. The severity of the phenotype depends on the extent of the deletion. Retinoblastoma is a malignant tumor in the retina and is the most common ocular cancer in children. The association of most cases of retinoblastoma with an interstitial del(13q) has led to the localization of the retinoblastoma gene in 13q14. We report a case of a boy aged 8 referred for cytogenetic studies, presenting with mild mental retardation, craniofacial dysmorphism, delayed intrauterine growth (IUGR) and retinoblastoma. The karyotype was obtained from peripheral blood lymphocyte cultures using high-resolution GTG banding and standard techniques. Fluorescence in situ hybridization was performed using the LSI 13 (RB1) probe (Vysis) for region 13q14 spanning the RB1 gene. The chromosomal analysis revealed a large interstitial deletion of the long arm of chromosome 13. Although the exact breakpoints were difficult to establish, the deleted region did not appear to encompass the band which includes the retinoblastoma gene. Molecular cytogenetic techniques showed that the retinoblastoma gene was deleted. This confirmed the clinical indication of retinoblastoma and defined the deletion breakpoints more precisely. Final karyotype: 46,XY,del(13)(q13q14.3).ish del(13) (q14.1q14.3)(RB1−). Except for the presence of IUGR, the clinical description of this patient is in agreement with other reports in the literature. We would like to emphasize the importance of detailed clinical information that, together with classical and molecular cytogenetic techniques, could be useful in better defining the breakpoints, establishing correct genotype/phenotype correlation and thus providing appropriate genetic counselling. The blood samples of the parents were requested for karyotype analysis in order to clarify this chromosome deletion

A "de novo" inv dup del(6q) - a case report

Abstrat publicado em: Chromosome Research. 2003;21(Suppl 1):S1–S168. doi:10.1007/s10577-013-9364-

A de novo complex chromosome rearrangement (CCR) involving chromosome 5, 6 and 15

Abstrat publicado em: Chromosome Research. 2003;21(Suppl 1):S1–S168. doi:10.1007/s10577-013-9364-

Detection of subtelomeric rearrangements in 1180 patients: FISH and MLPA contribution

Mental retardation (MR) is a major social, educational, and health problem affecting 3% of the population. Subtelomeric chromosome aberrations are one of the major causes of MR with or without multiple anomalies; previous studies have shown that these rearrangements are responsible for 3-6% of unexplained mental retardation. Between 2000-2010 in the Cytogenetics Unit, Centro de Genética Médica Jacinto de Magalhães, INSA (Portugal), the subtelomeric regions of all the chromosomes were analysed in 1180 individuals, whose karyotype had been considered normal. The reasons for referral included (i) psychomotor development delay or (ii) mental retardation with or without dysmorphisms. Until 2007 the analysis of metaphases, obtained from cultured lymphocytes following standard protocols, were performed by "Fluorescence in situ hybridization” (FISH): the first kit to be used was the Chromoprobe Multiprobe-TM (Cytocell) kit (until 2005), which was followed by the TotelVysion Multi-Color FISH Probe (Vysis). In 2007 the "Multiplex Ligation dependent Probe Amplification” (MLPA) was implemented in the laboratory, using kits P036 and P070 (MRC-Holland). All the unbalanced cases detected by MLPA were confirmed by FISH. Of a total of 1180 individuals, 62 (5.3%) showed chromosomal alterations: 60 in the subtelomeric regions and 2 in the control regions. It was not possible to perform any familial studies in 12 of the 62 cases (1.0%) and therefore the results were considered inconclusive. In the other 50 abnormal cases, the parental investigation allowed us to conclude that 30 (2.5%) of these patients had chromosomal abnormalities “de novo” that might be responsible for the clinical phenotype; the remaining 20 possibly abnormal cases (1.7%) were considered polymorphisms without pathological significance, since the apparent deletion or duplication had been inherited from phenotypically normal parents. The authors compare the results obtained in the individuals in the present study with literature reports and highlight the advantages/disadvantages of each technique

Chromosome 1p36 deletion syndrome: a report on 4 cases

Chromosome 1p36 deletion syndrome (MIM #607872) was first described in 1997 by Shapira et al. This condition is compatible with a monosomy of the 1p36 band in the distal region of the short arm of chromosome 1 and is the most common terminal deletion in humans, with an estimated prevalence of approximately 1 in 5,000 live births. This constitutional deletion is associated with mental retardation, developmental delay, seizures, hypotonia and heart defects. The syndrome is also characterized by several distinct dysmorphic features, including large anterior fontanels, microcephaly, brachycephaly, deep-set eyes, flat nose and nasal bridge, and pointed chin. The 1p36 band is not very clearly visible using classical cytogenetics, and it is therefore difficult to detect these deletions in banded karyotypes. Fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) analysis have increasingly been used, in addition to classical cytogenetic analysis, in children with mental retardation in order to identify this chromosomal abnormality. The authors present four patients between 1 month and 14 years of age with apparently normal karyotypes. Using molecular cytogenetic techniques, all cases showed a “pure” 1p36 deletion: three were detected by FISH (CEB108/T7, located at 1p36.3, Vysis) and are “de novo”; the fourth was detected by MLPA (P036 and P070, MRC Holland) analysis, and its origin is still unknown. The phenotypes of these patients are described and compared with other cases having this syndrome, described in the literature. We also emphasize the importance of good clinical characterization in order to establish the best cytogenetic strategy to assure accurate diagnosis

Prenatal diagnosis of a partial dup (16p) due to a rare recombinant resulting from a paternal intrachromosomal insertion

Poster: 10.P7Chromosomal rearrangements involving three break-points are relatively rare, about 1/5,000 live births. When a chromosomal segment is moved from one part of a chromosome into another part of the same chromosome, it is considered an intrachromosomal insertion; the orientation of the inserted material in relation to the centromere may remain the same, resulting in a direct insertion, or reversed, resulting in an inverted insertion. A single crossover in the gametogenesis between any of the three breakpoints may result in unbalanced recombinants, leading to phenotypic consequences in the offspring. Partial trisomy 16p is a rare chromosomal imbalance characterized by mental retardation, prenatal and post-natal growth deficiency, facial anomalies, cleft palate, congenital heart defects, and urogenital anomalies. Previous studies have established that the phenotype of this condition is not related to the extension of the duplicated segment and that the region 16p13.1–p13.3 is critical in determining this disorder. We report on a prenatal diagnosis performed at 14 weeks. The fetus presented with an increased fetal nuchal translucency and thus was referred for con- ventional cytogenetic studies. The chromosomal analysis of the amniotic fluid cells revealed a structurally abnormal chromosome 16, with additional material on 16q. The maternal karyotype was normal, but the father carried an intrachromosomal insertion in chromosome 16: a between-arm insertion of a small segment of the short arm into the distal region of the long arm. To characterize the extension of the imbalance in the fetus, chromosome comparative genomic hybridization (cCGH) analysis was performed. Fetus karyotype: 46,XY,rec(16)dup(16p)ins(16) (q24p13.2p13.3)pat.ish cgh dup(16)(p13.2p13.3). The authors emphasize the rarity of this case, explain its possible formation mechanism and compare the fetal phenotype (available after autopsy) with similar cases described in the literatur

LOCUS (LOng Covid-Understanding Symptoms, events and use of services in Portugal): A three-component study protocol

Study ProtocolApproximately 10% of patients experience symptoms of Post COVID-19 Condition (PCC) after a SARS-CoV-2 infection. Akin acute COVID-19, PCC may impact a multitude of organs and systems, such as the cardiovascular, respiratory, musculoskeletal, and neurological systems. The frequency and associated risk factors of PCC are still unclear among both community and hospital settings in individuals with a history of COVID-19. The LOCUS study was designed to clarify the PCC’s burden and associated risk factors. LOCUS is a multi-component study that encompasses three complementary building blocks. The “Cardiovascular and respiratory events following COVID-19” component is set to estimate the incidence of cardiovascular and respiratory events after COVID-19 in eight Portuguese hospitals via electronic health records consultation. The “Physical and mental symptoms following COVID-19” component aims to address the community prevalence of self-reported PCC symptoms through a questionnaire-based approach. Finally, the "Treating and living with Post COVID-19 Condition" component will employ semi-structured interviews and focus groups to characterise reported experiences of using or working in healthcare and community services for the treatment of PCC symptoms. This multi-component study represents an innovative approach to exploring the health consequences of PCC. Its results are expected to provide a key contribution to the optimisation of healthcare services design.This study is sponsored by Pfizer (grant code #68639655).info:eu-repo/semantics/publishedVersio