Clinical and cytogenetic profile of Fanconi anemia diagnosed after implementation of mitomycin C cytogenetic test in the state of Pernambuco, Brazil

ABSTRACT Introduction: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosomal instability and increased predisposition to malignancy. The diagnosis of FA requires clinical evaluation, confirmation of chromosomal fragility and/or analysis of genetic mutations. Therefore, this study aims to identify the clinical profile of patients with FA in the state of Pernambuco, Brazil. Method: We analyzed 100 individuals referred from the major hematology and bone marrow (BM) transplant centers in the state of Pernambuco, Brazil, between the years 2018 and 2022. The diagnosis of FA was performed using the mitomycin C chromosomal fragility test, clinical data and classical and molecular cytogenetic analyses. Results: We enrolled a total of 16 patients with FA to comprise this study. Most of these individuals (87.5%) came from the Agreste and Sertão regions of Pernambuco. We observed a slight female prevalence of FA (1.3:1). The primary clinical and laboratory findings were café au lait spots (62.5%) and bone abnormalities (53%, mainly thumb deformities [40%]). We performed BM cytogenetic analysis for eight patients - seven showed no chromosomal abnormalities and one presented the karyotype 47,XY,+21 [15]. Conclusions: Our results are important to promote public health measures for the early diagnosis of FA, as well as to foster the engagement of a multidisciplinary group in the treatment of this disease.

Clinical and cytogenetic profile of Fanconi anemia diagnosed after implementation of mitomycin C cytogenetic test in the state of Pernambuco, Brazil.

INTRODUCTION: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosomal instability and increased predisposition to malignancy. The diagnosis of FA requires clinical evaluation, confirmation of chromosomal fragility and/or analysis of genetic mutations. Therefore, this study aims to identify the clinical profile of patients with FA in the state of Pernambuco, Brazil. METHOD: We analyzed 100 individuals referred from the major hematology and bone marrow (BM) transplant centers in the state of Pernambuco, Brazil, between the years 2018 and 2022. The diagnosis of FA was performed using the mitomycin C chromosomal fragility test, clinical data and classical and molecular cytogenetic analyses. RESULTS: We enrolled a total of 16 patients with FA to comprise this study. Most of these individuals (87.5%) came from the Agreste and Sertão regions of Pernambuco. We observed a slight female prevalence of FA (1.3:1). The primary clinical and laboratory findings were café au lait spots (62.5%) and bone abnormalities (53%, mainly thumb deformities [40%]). We performed BM cytogenetic analysis for eight patients - seven showed no chromosomal abnormalities and one presented the karyotype 47,XY,+21 [15]. CONCLUSIONS: Our results are important to promote public health measures for the early diagnosis of FA, as well as to foster the engagement of a multidisciplinary group in the treatment of this disease.

Hemophagocytic syndrome in a patient with Fanconi anemia and VACTERL association / Síndrome hemofagocítica em paciente com anemia de Fanconi e associação VACTERL

INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.

INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.

Antioxidant and in vitro cytogenotoxic properties of Amburana cearensis (Allemão) A.C.Sm. leaf extract.

Amburana cearensis leaves have been used in folk medicine to treat respiratory diseases and inflammations. This study aimed to evaluate the biological potential of A. cearensis leaves by antioxidant and in vitro cytogenotoxic analyses of ethanolic crude extract (EE) and its fractions in healthy human cells. The EE was obtained by percolation, followed by fractionation using dichloromethane, cyclohexane, ethyl acetate (EtOAc), and methanol (MeOH) as organic solvents. Extract and all fractions were evaluated for their antioxidant potential by DPPH and reducing power tests. In vitro cytotoxic activity was determined in human peripheral blood mononuclear cells by MTT assay for the extract, EtOAc and MeOH fractions. In turn, the genotoxic activity was determined in human lymphocytes by the Cytokinesis Block Micronucleus assay only for the EtOAc fraction. Only EtOAc fraction was analyzed via gas chromatography coupled to mass spectrometry due to its higher biological activity. Considering the antioxidant potential, the EtOAc fraction was most effective in DPPH (EC50 43.37 µg/mL) and reducing power (EC50 89.80 µg/mL) assays. GC-MS analysis of the EtOAc fraction led to the identification of guaiacol, 2,3-dihydro-benzofuran, 2-methoxy-4-vinylphenol, isovanillic acid methyl ester, 4-hydroxybenzaldehyde, and 4-(ethoxymethyl)-phenol. The EE (400-1000 µg/mL), EtOAc (≤150 µg/mL) and MeOH (50 and 150-600 µg/mL) fractions were not cytotoxic by MTT test. Additionally, the EtOAc fraction (100-400 µg/mL) did not induce significant genotoxic damage. Concentrations of the EtOAc fraction with antioxidant activity showed no cytotoxicity, nor genotoxicity potential, indicating them as a nontoxic natural antioxidant source.

Complete mitochondrial genome of the greater round-eared bat, Tonatia bidens (Chiroptera: Phyllostomidae) from Brazil and phylogenetic relationships within the family.

The greater round-eared bat, Tonatia bidens, is a locally rare species belonging to the highly diverse family Phyllostomidae. In this study, the complete mitogenome of T. bidens was sequenced using optimized protocols of DNA extraction from fixed cells originally prepared for cytogenetic studies. Here we present the complete mitogenome and place our results in a phylogenetic context with other data generated for the family Phyllostomidae. The circular genome had 16,717 bp in size, comprising 37 genes and GC content of 42.24%. Furthermore, the phylogenetic tree indicated a well-supported relationship between the representatives of Tonatia into the subfamily Phyllostominae.

Chromosome Painting in Lonchorhina aurita Sheds Light onto the Controversial Phylogenetic Position of Sword-Nosed Bats (Chiroptera, Phyllostomidae).

The subfamily Lonchorhininae encompasses 6 species of sword-nosed bats (Lonchorhina) and is one of the most problematic lineages in the Neotropical leaf-nosed bats (Phyllostomidae) phylogeny. There are at least 5 different hypotheses to explain when the subfamily diverged from the remaining phyllostomids, but none with robust statistical support. Here, we generated a chromosome painting homology map of Lonchorhina aurita karyotype (2n = 32 and FN = 60) using whole-chromosome probes of Macrotus californicus (MCA; 2n = 40 and FN = 60). We placed the karyotype changes of L. aurita in a phylogenetic context to discuss the most likely branching position of Lonchorhininae based on karyotypic evolution. We show that L. aurita has a derived karyotype with 24 segments homologous to the 20 MCA chromosomes used as probes. Comparative analyses between 7 published painted bats species across 4 phyllostomid subfamilies (Macrotinae, Phyllostominae, Glossophaginae, and Lonchophyllinae) revealed that one inversion (MCA 4inv) and one fusion (MCA 17 + 18) are shared derived features between the karyotypes of L. aurita and species of Phyllostominae not yet observed in other bats. Our data show that chromosomal homology maps may contribute with new insights into a long-standing phylogenetic debate that has endured for decades.

Calibration curves by 60Co with low dose rate are different in terms of dose estimation - a comparative study.

Biological dosimetry aims to estimate individual absorbed doses due ionizing radiation exposure. The dicentric chromosomes are considered the most specific biomarker for dose estimation. This study aimed to compare calibration curves for linear low energy transfer (LET) radiation built from low dose rates and whether they vary in terms of dose estimation. For that we did a search in the literature of all calibration curves produced with low dose rates and we simulated the dose estimation from pre-established dicentric's frequencies. The information on methodologies and cytogenetic results of each study were analyzed. As expected dose rate influence ß coefficients, especially at higher doses. However, we have seen that some doses were not statistically different but they should be, because there is a significant association between the productions of dicentrics and dose rate. This comparative study reinforced the robustness of the dicentric assay and its importance in biological dosimetry. We also emphasized that the dose rate was an important factor in dose estimations. Thus, intercomparison exercises should take into account the dose rates of the participating laboratories, because the dose rates might explain why some results of estimated doses fall outside the recommendations.

Comparative study of micronucleus assays and dicentric plus ring chromosomes for dose assessment in particular cases of partial-body exposure.

Purpose: The goal was to compare the micronucleus (MN) and dicentric plus ring chromosomes (D + R) assays for dose assessment in cases of partial body irradiations (PBI). Materials and methods: We constructed calibration curves for each assay at doses ranging from 0 to 5 Gy of X-rays at dose rate of 0.275 Gy/min. To simulate partial-body exposures, blood samples from two donors were irradiated with 0.5, 1, 2 and 4 Gy and the ratios of irradiated to unirradiated blood were 25, 50, and 100%. Different tests were used to confirm if all samples were overdispersed or zero-inflated and for partial-body dose assessment we used the Qdr, Dolphin and Bayesian model. Results: In our samples for D + R calibration curve, practically all doses agreed with Poisson assumption, but MN exhibited overdispersed and zero-inflated cellular distributions. The exact Poisson tests and zero-inflated tests demonstrate that virtually all samples of D + R from PBI simulation fit the Poisson distribution and were not zero-inflated, but the MN samples were also overdispersed and zero-inflated. In the partial-body estimation, when Qdr and Dolphin methods were used the D + R results were better than MN, but the doses estimation defined by the Bayesian methodology were more accurate than the classical methods. Conclusions: Dicentric chromosomes continue to prove to be the best biological marker for dose assessment. However exposure scenarios of partial-body estimation, overdispersion and zero-inflation may not occur, it being a critical point not only for dose assessment, but also to confirm partial-body exposure. MN could be used as alternative assay for partial-body dose estimation, but in case of an accident without any information, the MN assay could not define whether the accident was a whole-body irradiation (WBI) or a PBI.

CTLA-4 gene polymorphisms are associated with obesity in Turner Syndrome.

Turner syndrome (TS) is characterized by a set of clinical conditions, including autoimmune/inflammatory diseases and infectious conditions, that can compromise a patient's quality of life. Here we assessed polymorphisms in CTLA-4 +49A/G (rs231775), PTPN22 +1858G/A (rs2476601), and MBL2 -550 (H/L) (rs11003125), -221(X/Y) (rs7096206) and exon 1 (A/O) in women from northeastern Brazil to determine whether polymorphisms within these key immune response genes confer differential susceptibility to clinical conditions in TS. A case-control genetic association study was performed, including 86 female TS patients and 179 healthy women. An association was observed for the A/G genotype of CTLA-4 +49A/G in TS patients (p=0.043, odds ratio [OR]=0.54). In addition, an association between the CTLA-4 G/G genotype and obesity was detected in TS patients (p=0.02, OR=6.04). Regarding, the -550(H/L) polymorphism in the MBL2 promoter, the frequency of the H/L genotype was significantly higher in the TS group than healthy controls (p=0.01, OR=1.96). The H/H genotype indicated a protective effect in TS patients (p=0.01, OR=0.23). No differences were observed in the distribution of -221(X/Y), MBL2 exon 1 variants, and PTPN22 +1858G/A in any assessed groups. CTLA-4 variants are potentially involved in obesity in this cohort of TS patients from northeastern Brazil.

Evaluation of the genotoxic effects of formocresol application in vital pulp therapy of primary teeth: a clinical study and meta-analysis.

OBJECTIVES: This in vivo research investigated whether pulp treatments using formocresol for 7 days would cause mutagenic changes in children's lymphocytes. MATERIALS AND METHODS: The mutagenicity was tested in lymphocyte cultures established from the peripheral blood of children living in Brazil. The samples consisted of 2000 cells from teeth undergoing formocresol pulpotomies in which the formocresol pellet was sealed in the primary tooth for 7 days. It was removed on the seventh day, the base was placed, and the tooth was restored. Two venous blood samples (6-8 ml) were collected from each child; the first was prior to pulp therapy, and the second was 7 days later. Two thousand metaphases were analyzed. The level of significance adopted for the statistics was P < 0.05, and a random effects meta-analysis was performed combining this and two previous studies. RESULTS: There was no significant difference found in the metaphase analysis between the blood samples taken before and after the pulpotomy treatment (Wilcoxon signed rank test); however, the meta-analysis showed a significant difference between the combined studies. CONCLUSIONS: This study did not reveal any mutagenic effects, but based on the combined meta-analysis, we recommend the careful use of formocresol. CLINICAL RELEVANCE: This research helps to bring scientific evidence of the safe use of formocresol in deciduous pulpotomy treatments.

Perfil dos estudantes que ingressam no curso de Odontologia: motivos da escolha / Profile of students entering Dentistry school: reasons for choosing it

O objetivo deste estudo, com recorte transversal de natureza quantitativa, foi avaliar o perfil, a percepção e o motivo da escolha pelo curso de Odontologia em uma faculdade particular de Campinas (SP). Do total de 153 alunos matriculados em 2016, 102 (66,7%) aceitaram participar da pesquisa. O instrumento de pesquisa foi um questionário estruturado, autoaplicável, com 22 questões que versavam sobre perfil socioeconômico, demográfico, percepção sobre o curso e os motivos de sua escolha. Entre os respondentes, 81,4% eram do sexo feminino. A faixa etária de 17 a 20 anos predominou (67,3%), sendo a maioria solteiros (89,3%), tendo cursado ensino médio em escola particular (80,4%), com renda familiar acima de R$ 8.800,00 (54,0%). Quando abordados sobre o motivo da escolha pelo curso, 61,7% optaram por ser da área da saúde; e 29,4% sofreram influência de um dentista. Quanto à pretensão profissional, 6,8% querem trabalhar somente no setor público, 47,0% querem ser assalariados e montar seu próprio negócio e 38% querem trabalhar de forma autônoma em consultório. Sobre o curso, 62,8% se declararam satisfeitos com o corpo docente; 72,5%, com a matriz curricular, e a maioria (70,5%) deseja cursar especialização após a graduação. Sobre a escolha, 97,0% estão satisfeitos; e 96,0% se sentem preparados para enfrentar o mercado de trabalho. A percepção dos respondentes é positiva quanto à formação. Há o reconhecimento da tendência de assalariamento na profissão, embora demonstrem o desejo de atuação no setor privado (AU).

The aim of the present cross-sectional, quantitative study was to evaluate the profile of students on the Dentistry course of a private college in Campinas (São Paulo) and their perception of and reasons for choosing such a course. Of the 153 students enrolled in 2016, 102 (66.7%) agreed to participate in the study. The research tool was a structured, self-administered questionnaire featuring 22 questions that dealt with socioeconomic and demographic profile, perception of the course and reasons for choosing it. Of those who responded, 81.4% were female. The 17 to 20 year-old age group predominated (67.3%), while most of the sample were single (89.3%), had attended a private high school (80.4%), and had a family income of over R$ 8,800.00 (54.0%). When asked about the reason for choosing the course, 61.7% said it was because it was part of the area of health, while 29.4% were influenced by a dentist. Regarding professional intentions, 6.8% wanted to work in the public sector only, 47.0% wanted to be salaried employees and set up their own business and 38% wanted to be self-employed in a dental surgery. A total of 62.8% declared themselves satisfied with the teaching staff of the course; 72.5% said they were satisfied with the curriculum, and the majority (70.5%) planned to do a specialization course after graduation. With regard to their choice, 97.0% were satisfied; while 96.0% felt prepared to enter the job market. The perception of the respondents about their training was positive. A trend towards salaried work in the profession was noted, although a desire to work in the private sector was also noted (AU).

B Chromosome Variants of the Grasshopper Xyleus discoideus angulatus Are Potentially Derived from Pericentromeric DNA.

B chromosomes, extra elements present in the karyotypes of some eukaryote species, have been described in the grasshopper Xyleus discoideus angulatus. Although some studies have proposed an autosomal origin of the B chromosome in X. d. angulatus, little is known about its repetitive DNA composition and evolutionary dynamics. The aim of the present work was to shed light on the B chromosome evolution in X. d. angulatus by cytogenetic analysis of 27 populations from Pernambuco and Ceará states (Brazil). The frequency of B chromosomes in the different populations was determined, and chromosome measurements and fluorescence in situ hybridization (FISH) with C0t-DNA and telomeric and B chromosome sequences were performed in cells from B-carrying individuals. The results revealed variations in B chromosome prevalence among the populations and showed that some B chromosomes were smaller in certain populations. FISH produced similar patterns for the C0t-DNA probe in all hybridized individuals, whereas telomeric and B chromosome probes, obtained by microdissection, exhibited variations in their distribution. These results indicate the presence of 3 morphotypes of B chromosomes in X. d. angulatus, with variation in repetitive DNA composition during their evolution. In this species, B chromosomes have an intraspecific origin and probably arose from the pericentromeric region of A chromosomes.

Centromeric enrichment of LINE-1 retrotransposons and its significance for the chromosome evolution of Phyllostomid bats.

Despite their ubiquitous incidence, little is known about the chromosomal distribution of long interspersed elements (LINEs) in mammalian genomes. Phyllostomid bats, characterized by lineages with distinct trends of chromosomal evolution coupled with remarkable ecological and taxonomic diversity, represent good models to understand how these repetitive sequences contribute to the evolution of genome architecture and its link to lineage diversification. To test the hypothesis that LINE-1 sequences were important modifiers of bat genome architecture, we characterized the distribution of LINE-1-derived sequences on genomes of 13 phyllostomid species within a phylogenetic framework. We found massive accumulation of LINE-1 elements in the centromeres of most species: a rare phenomenon on mammalian genomes. We hypothesize that expansion of these elements has occurred early in the radiation of phyllostomids and recurred episodically. LINE-1 expansions on centromeric heterochromatin probably spurred chromosomal change before the radiation of phyllostomids into the extant 11 subfamilies and contributed to the high degree of karyotypic variation observed among different lineages. Understanding centromere architecture in a variety of taxa promises to explain how lineage-specific changes on centromere structure can contribute to karyotypic diversity while not disrupting functional constraints for proper cell division.

MMP20 rs1784418 Protects Certain Populations against Caries.

This work aimed to further evaluate the association of MMP20 rs1784418 C>T and dental caries experience with the hypothesis that MMP20 rs1784418 C>T is a risk factor for dental caries. 184 children 4-7 years of age had their caries experience determined and buccal cheek swabs collected for DNA extraction to test for association with the MMP20 rs1784418 C>T using standard statistical approaches. A meta-analytic approach was also implemented to compile previous discrepant reports of the same association. We found an association between MMP20 rs1784418 C>T and dental caries experience in primary dentition (p = 0.01). The meta-analysis showed that this association appears to favor individuals born in Brazil and not Turkey. MMP20 rs1784418 C>T appears to protect against dental caries, but its effects are likely to be more marked in certain populations.

Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome.

Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal chromosomal segregation. Previous investigations of this association have produced controversial results. Here we performed a case-control study in patients with Turner syndrome (TS) to determine the effects of genetic polymorphisms of folate pathway genes as potential risk factors for somatic chromosomal nondisjunction. TS is a useful model for this investigation because patients with TS show a high frequency of chromosome mosaicism. Here we investigated the possible association of polymorphisms of the MTHFR gene with TS risk, which has been previously investigated with controversial results. We also examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the first time. The risk was evaluated according to allelic and genotype (independent and combined) frequencies among 70 patients with TS and 144 age-matched healthy control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR-ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and TYMS 2R/3R-alone or in combinations-were not associated with the risk of chromosomal aneuploidy in TS. In conclusion, our present findings did not support a link between impaired folate metabolism and abnormal chromosome segregation leading to somatic nondisjunction in TS patients.

Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case.

Turner syndrome (TS) is a common genetic disorder in females associated with the absence of complete or parts of a second sex chromosome. In 5-12% of patients, mosaicism for a cell line with a normal or structurally abnormal Y chromosome is identified. The presence of Y-chromosome material is of medical importance because it results in an increased risk of developing gonadal tumours and virilisation. Molecular study and fluorescence in situ hybridisation approaches were used to study 74 Brazilian TS patients in order to determine the frequency of hidden Y-chromosome mosaicism, and to infer the potential risk of developing malignancies. Additionally, we describe one TS girl with a very uncommon karyotype 46,X,der(X)t(X;Y)(p22.3?2;q11.23) comprising a partial monosomy of Xp22.3?2 together with a partial monosomy of Yq11.23. The presence of cryptic Y-chromosome-specific sequences was detected in 2.7% of the cases. All patients with Y-chromosome-positive sequences showed normal female genitalia with no signs of virilisation. Indeed, the clinical data from Y-chromosome-positive patients was very similar to those with Y-negative results. Therefore, we recommend that the search for hidden Y-chromosome mosaicism should be carried out in all TS cases and not be limited to virilised patients or carriers of a specific karyotype.

Reduced folate carrier-1 G80a gene polymorphism is associated with neuroblastoma's development.

Neuroblastoma is a malignant embryonal tumor of neural crest cells that give rise to the sympathetic nervous system, responsible for 10-70% of all cases of childhood cancer. Because of its early appearance, it has been suggested that risk factors active in the prenatal can be associated with the pathogenesis of neuroblastoma. The aim of this study was to investigate whether the genetic polymorphisms MTHFR C677T and A1298C, MTR A2756G, TYMS 2R/3R and SLC19A1 G80A, involved in folate metabolism, increase the risk of neuroblastoma in Brazilian children. This study comprised 31 Brazilian children (0-14 years old) diagnosed with neuroblastoma compared with 92 controls. Investigation of polymorphisms MTHFR C677T, MTR A2756G and SLC19A1 A80G was performed using PCR-RFLP, the TYMS 2R/3R using PCR and MTHFR A1298C using AS-PCR. The SLC19A1 A80A genotype was significantly associated with the development of neuroblastoma, compared with the control group (Williams G-Test = 0.0286; OR = 5.1667; 95% CI = 1.4481-18.4338; p = 0.0175). When analyzed together, the 80AG+AA genotypes showed a trend toward association (OR = 3.3033; 95% CI = 1.0586-10.3080; p = 0.0563). Our results suggest that individuals carriers of genotype AA for the SLC19A1 gene present risk for the development of neuroblastoma and possibly have difficulty in absorption of folic acid by the cells, and this may adversely affect the metabolism of folate causing genomic instability and promoting the development of cancer. This is the first retrospective/prospective study to examine the relationship between polymorphisms of folate pathway genes and risk of neuroblastoma.

Patterns of rDNA and telomeric sequences diversification: contribution to repetitive DNA organization in Phyllostomidae bats.

Chromosomal organization and the evolution of genome architecture can be investigated by physical mapping of the genes for 45S and 5S ribosomal DNAs (rDNAs) and by the analysis of telomeric sequences. We studied 12 species of bats belonging to four subfamilies of the family Phyllostomidae in order to correlate patterns of distribution of heterochromatin and the multigene families for rDNA. The number of clusters for 45S gene ranged from one to three pairs, with exclusively location in autosomes, except for Carollia perspicillata that had in X chromosome. The 5S gene all the species studied had only one site located on an autosomal pair. In no species the 45S and 5S genes collocated. The fluorescence in situ hybridization (FISH) probe for telomeric sequences revealed fluorescence on all telomeres in all species, except in Carollia perspicillata. Non-telomeric sites in the pericentromeric region of the chromosomes were observed in most species, ranged from one to 12 pairs. Most interstitial telomeric sequences were coincident with heterochromatic regions. The results obtained in the present work indicate that different evolutionary mechanisms are acting in Phyllostomidae genome architecture, as well as the occurrence of Robertsonian fusion during the chromosomal evolution of bats without a loss of telomeric sequences. These data contribute to understanding the organization of multigene families and telomeric sequences on bat genome as well as the chromosomal evolutionary history of Phyllostomidae bats.

Extra Copies of der(21)t(12;21) plus Deletion of ETV6 Gene due to dic(12;18) in B-Cell Precursor ALL with Poor Outcome.

Acute lymphoblastic leukemia (ALL), CD10+ B-cell precursor, represents the most frequent type of childhood ALL from 3 to 6 years of age. The t(12;21)(p13;q22) occurs in 25% of cases of B-cell precursor ALL, it is rare in children less than 24 months and have been related to good prognosis. Some relapse cases and unfavorable prognosis in ALL CD10+ are associated with t(12;21) bearing additional aberrations as extra copies of chromosome 21 and ETV6 gene loss. This report describes the case of a 15 month-year old girl, who displayed a karyotype with addition on chromosome 12p plus trisomy 10 and tetrasomy of chromosome 21. Molecular cytogenetic studies revealed two extra copies of the der(21) t(12;21), trisomy 10 and deletion of the second ETV6 gene due to the dic(12;18). These findings show the great importance of molecular cytogenetic studies to clarify complex karyotypes, to define prognostic, to carry out risk group stratification and to support correctly disease treatment in childhood acute lymphoblastic leukemia.

A Locus Identified on Chromosome18P11.31 is Associated with Hippocampal Abnormalities in a Family with Mesial Temporal Lobe Epilepsy.

We aimed to identify the region harboring a putative candidate gene associated with hippocampal abnormalities (HAb) in a family with mesial temporal lobe epilepsy (MTLE). Genome-wide scan was performed in one large kindred with MTLE using a total of 332 microsatellite markers at ∼12 cM intervals. An additional 13 markers were genotyped in the candidate region. Phenotypic classes were defined according to the presence of hippocampal atrophy and/or hyperintense hippocampal T2 signal detected on magnetic resonance imaging. We identified a significant positive LOD score on chromosome 18p11.31 with a Z(max) of 3.12 at D18S452. Multipoint LOD scores and haplotype analyses localized the candidate locus within a 6-cM interval flanked by D18S976 and D18S967. We present here evidence that HAb, which were previously related mainly to environmental risk factors, may be influenced by genetic predisposition. This finding may have major impact in the study of the mechanisms underlying abnormalities in mesial temporal lobe structures and their relationship with MTLE.