Chromothripsis with at least 12 breaks at 1p36.33-p35.3 in a boy with multiple congenital anomalies.

Terminal deletion in the short arm of chromosome 1 results in a disorder described as 1p36 deletion syndrome. The resulting phenotype varies among patients including mental retardation, developmental delay, sensorineural hearing loss, seizures, heart defects, and distinct facies. In the present case, we performed array-comparative genomic hybridization in a boy with multiple congenital malformations presenting some features overlapping the 1p36 deletion phenotype for whom chromosomal analysis did not reveal a terminal deletion in 1p. Results showed complex chromosome rearrangements involving the 1p36.33-p35.3 region. While the mechanism of origin of these rearrangements is still unclear, chromothripsis-a single catastrophic event leading to shattering chromosomes or chromosome regions and rejoining of the segments-has been described to occur in a fraction of cancers. The presence of at least 12 clustered breaks at 1p and apparent lack of mosaicism in the present case suggests that a single event like chromothripsis occurred. This finding suggests that chromothripsis is responsible for some constitutive complex chromosome rearrangements.

Microphthalmia, Linear Skin Defects, Callosal Agenesis, and Cleft Palate in a Patient with Deletion at Xp22.3p22.2.

The authors describe the clinical findings observed in a Brazilian girl that are suggestive of microphthalmia and linear skin defects (MLS) also known as MIDAS syndrome (OMIM #309801). She also presented with short stature, agenesis of corpus callosum, cleft palate, enamel defects, and genitourinary anomalies, which are rarely reported within the clinical spectrum of MLS. The 11,5 Mb deletion in Xp22.3p22.2 observed in the patient includes the entire HCCS gene (responsible for the MLS phenotype) and also encompasses several other genes involved with behavioral phenotypes, craniofacial and central nervous system development such as MID1, NLGN4X, AMELX , ARHGAP6, and TBL1X. The whole clinical features of our proband possibly represents an unusual MLS syndromic phenotype caused by an Xp22.3p22.2 continuous gene deletion.

First description and evaluation of SNPs in the ADH and ALDH genes in a population of alcoholics in Central-West Brazil.

Worldwide, different studies have reported an association of alcohol-use disorder (AUD) with different types of Single Nucleotide Polymorphisms (SNPs) in the genes for aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH). In Brazil, there is little information about the occurrence of these SNPs in the AUD population and an absence of studies characterizing the population in the Central-West Region of Brazil. Actually, in Brazil, there are more than 4 million people with AUD. Despite the major health hazards of AUD, information on alcohol consumption and its consequences are not well understood. Therefore, it is extremely important to characterize these SNPs for the better understanding of AUD as a genetic disease in the Brazilian population. The present study, unlike other studies in other countries, is done with a subject population that shows a significant amount of racial homogenization. We evaluated the presence of SNPs in the ADH (ADH1B, ADH1C, and ADH4) and ALDH (ALDH2) genes in alcohol users of Goiânia, State of Goiás - Brazil, and then we established a possible relationship with AUD by allelic and genotypic study. This study was conducted with a population of people with AUD (n = 99) from Goiás Alcohol Dependence Recovery Center (GO CEREA) and Psychosocial Care Center for Alcohol and Drugs (CAPS AD), and with a population of people without AUD as controls (n = 100). DNA was extracted from whole-blood samples and the genotyping was performed using TaqMan® SNP genotyping assays. For characterization and evaluation of SNPs in the population, genotype frequency, allele frequency, haplotype frequency, Hardy-Weinberg equilibrium, and linkage disequilibrium were analyzed. Statistical analyses were calculated by GENEPOP 4.5 and Haploview software. The allele 1 was considered as "wild" (or *1) and allele 2 as mutant (or *2). Significant differences were found for ADH1B*, ADH4*2, and ALDH2*2 SNPs when the genotype and allele frequencies were analyzed. In addition, four haplotypes were observed between ADH1B*2 and ADH1C*2 through linkage disequilibrium analysis. The genetic variants may be associated with protection against AUD in the population studied.

Multisystem Involvement in a Patient with a PTCH1 Mutation: Clinical and Imaging Findings.

In this article, we report on a Brazilian female patient born to consanguineous parents and presenting with alobar holoprosencephaly, severe eye involvement, and unusual skin hyperpigmented lesions. She was found to have a mutation (c.2240T > C; p.Val751Gly) in exon 15 of the PTCH1 gene. Mutations in this gene are associated with the nevoid basal cell carcinoma syndrome (NBCCS, OMIM 109400) and, in other instances, with holoprosencephaly (holoprosencephaly-7, OMIM 610828). Severe eye involvement ranging from orbital coloboma to microphthalmia has been seldom reported in patients with NBCCS with PTCH1 mutations. To our knowledge, this is the first report of an individual with central nervous system, skin, and eye manifestations due to a PTCH1 mutation. Mechanisms involved in these multisystem manifestations are discussed.

Congenital Heart Disease Revealing Familial 22q11 Deletion Syndrome

Abstract Congenital heart defects are the most common birth defects and the leading cause of mortality in the first year of life. It is well known that the 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and that congenial heart diseases (CHDs) are one of the most common phenotypic manifestations. However, it should be noted that the 22q11 deletion was also found in a significant number of patients with isolated CHD. The 22q11DS phenotype may include cardiovascular anomalies, palatal abnormalities, nasal voice, immune deficiency, endocrine dysfunctions, a varying degree of cognitive deficits and intellectual disabilities, velopharyngeal insufficiency, and characteristic craniofacial dysmorphism. This condition affects about 1 in 4,000 live births, making 22q11DS the most common microdeletion syndrome in humans. Here we describe the cases of three children who were referred to the clinical hospital center with the diagnosis of CHD, but with no direct signs of 22q11DS. Investigation of familial data led us to suspect that the mothers could be carriers of 22q11DS. The multiplex ligation-dependent probe amplification (MLPA) testing confirmed that the patients and mothers exhibited 3 Mb 22q11 deletions, which justified the clinical signs in the mothers and the CHD in children. In the presence of a few characteristics that are common of a spectrum of some known syndromes, a familial examination can provide clues to a definitive diagnosis, as well as to the prevention of diseases and genetic counseling of these patients.

Validation of a physical anthropology methodology using mandibles for gender estimation in a Brazilian population.

UNLABELLED: Validation studies of physical anthropology methods in the different population groups are extremely important, especially in cases in which the population variations may cause problems in the identification of a native individual by the application of norms developed for different communities. OBJECTIVE: This study aimed to estimate the gender of skeletons by application of the method of Oliveira, et al. (1995), previously used in a population sample from Northeast Brazil. MATERIAL AND METHODS: The accuracy of this method was assessed for a population from Southeast Brazil and validated by statistical tests. The method used two mandibular measurements, namely the bigonial distance and the mandibular ramus height. The sample was composed of 66 skulls and the method was applied by two examiners. The results were statistically analyzed by the paired t test, logistic discriminant analysis and logistic regression. RESULTS: The results demonstrated that the application of the method of Oliveira, et al. (1995) in this population achieved very different outcomes between genders, with 100% for females and only 11% for males, which may be explained by ethnic differences. However, statistical adjustment of measurement data for the population analyzed allowed accuracy of 76.47% for males and 78.13% for females, with the creation of a new discriminant formula. CONCLUSION: It was concluded that methods involving physical anthropology present high rate of accuracy for human identification, easy application, low cost and simplicity; however, the methodologies must be validated for the different populations due to differences in ethnic patterns, which are directly related to the phenotypic aspects. In this specific case, the method of Oliveira, et al. (1995) presented good accuracy and may be used for gender estimation in Brazil in two geographic regions, namely Northeast and Southeast; however, for other regions of the country (North, Central West and South), previous methodological adjustment is recommended as demonstrated in this study.

Sonic hedgehog (SHH) mutation in patients within the spectrum of holoprosencephaly.

Holoprosencephaly (HPE) is a malformation sequence where the cerebral hemispheres fail to separate into distinct left and right halves. It can be associated with midline structural anomalies of the central nervous system and/or face. SHH is the major gene implicated in HPE and it plays a critical role in early forebrain and central nervous system development. SHH is expressed in the human embryo in the notochord, the floorplate of the neural tube, and the posterior limb buds. In the present study we performed mutational analysis of the entire coding region of the SHH gene in 37 unrelated individuals with the HPE spectrum. Three different variants were found throughout the extent of the gene. No genotype-phenotype correlation is evident based on the type or position of the mutations. This study confirms the great genetic heterogeneity of the disease and the difficulty to establish genotype-phenotype correlations.

Validation of a physical anthropology methodology using mandibles for gender estimation in a Brazilian population

Validation studies of physical anthropology methods in the different population groups are extremely important, especially in cases in which the population variations may cause problems in the identification of a native individual by the application of norms developed for different communities. OBJECTIVE: This study aimed to estimate the gender of skeletons by application of the method of Oliveira, et al. (1995), previously used in a population sample from Northeast Brazil. MATERIAL AND METHODS: The accuracy of this method was assessed for a population from Southeast Brazil and validated by statistical tests. The method used two mandibular measurements, namely the bigonial distance and the mandibular ramus height. The sample was composed of 66 skulls and the method was applied by two examiners. The results were statistically analyzed by the paired t test, logistic discriminant analysis and logistic regression. RESULTS: The results demonstrated that the application of the method of Oliveira, et al. (1995) in this population achieved very different outcomes between genders, with 100% for females and only 11% for males, which may be explained by ethnic differences. However, statistical adjustment of measurement data for the population analyzed allowed accuracy of 76.47% for males and 78.13% for females, with the creation of a new discriminant formula. CONCLUSION: It was concluded that methods involving physical anthropology present high rate of accuracy for human identification, easy application, low cost and simplicity; however, the methodologies must be validated for the different populations due to differences in ethnic patterns, which are directly related to the phenotypic aspects. In this specific case, the method of Oliveira, et al. (1995) presented good accuracy and may be used for gender estimation in Brazil in two geographic regions, namely ...

Human identification analysis using PCR from the root portion of dental elements under different conditions of temperature and exposure time

Introduction and Objective: The main exogenous factors limiting the retrieval of information from human remains are fire and accidents involving high temperatures. Teeth, due to their relatively high degree of chemical and physical resistance, offer the possibility for the recovery of genetic material, becoming important in forensic cases. With the aim to contribute to a standardization of the protocols employed in DNA extraction and analysis, it was evaluated the integrity of DNA recovered from dental roots submitted to high temperatures, simulating what happens to burnt people. Material and methods: Extractions of genomic DNA were made from the dental root after exposure to high temperatures (600ºC, 800ºC and 1000ºC), during 10, 30 and 60 minutes. Results and Conclusion: After molecular analysis through PCR technique, it was verified that DNA amplification of the samples was not possible at any of the periods and temperatures analyzed.

Quality evaluation of DNA obtained from stored human saliva and its applicability to identification in Forensic Dentistry / Avaliação da qualidade do DNA extraído de saliva humana armazenada e sua aplicabilidade na identificação em Odontologia Legal

Purpose: This study evaluated the quality of DNA obtained from stored human saliva and its applicability to human identification. Methods: The saliva samples of 20 subjects, collected in the form of saliva in natura and from mouth swabs and stored at -20ºC, were analyzed. After 7 days, the DNA was extracted from the 40 saliva samples and subjected to PCR and electrophoresis. After 180 days, the technique was repeated with the 20 swab samples. Results: The first-stage results indicated that DNA was successfully extracted in 97.5% of reactions, 95% of saliva in natura and 100% of swab saliva samples, with no statistically significant difference between the forms of saliva. In the second phase, the result was positive for all 20 analyzed samples (100%). Subsequently, in order to analyze the quality of the DNA obtained from human saliva, the SIX3-2 gene was tested on the 20 mouth swab samples, and the PCR products were digested using the MbO1 restriction enzyme to evaluate polymorphisms in the ADRA-2 gene, with positive results for most samples. Conclusion: It was concluded that the quantity and quality of DNA from saliva and the techniques employed are adequate for forensic analysis of DNA.

Objetivo: Este trabalho objetivou avaliar a qualidade do DNA obtido de saliva humana armazenada e sua aplicabilidade da identificação de pessoas. Metodologia: Analisaram-se amostras salivares de n=20 sujeitos da pesquisa, coletadas nas formas de saliva in natura e de swab bucal, sendo armazenadas a 20ºC. Após 7 dias, o DNA foi extraído das 40 amostras de saliva e submetido à PCR e à eletroforese. Após 180 dias repetiu-se a técnica nas 20 amostras de swab. Resultados: Os resultados da primeira etapa indicaram que o DNA foi extraído com sucesso em 97,5% das reações, e, analisando-se separadamente, em 95% de saliva in natura e em 100% da saliva do swab, não havendo diferenças estatisticamente significantes entre as duas formas de saliva. Na segunda fase, o resultado foi positivo para as 20 amostras analisadas (100%). Posteriormente, para analisar a qualidade do DNA obtido da saliva humana, o gene SIX3-2 foi testado nas 20 amostras de swab bucal e foi feita a digestão do produto da PCR com a enzima de restrição MbO1 para avaliar polimorfismo do gene ADRA-2 obtendo-se resultados positivos para a maioria das amostras. Conclusão: Concluiu-se que a quantidade e a qualidade do DNA advindo de saliva e as técnicas empregadas estão adequadas à análise forense do DNA.