Spinocerebellar ataxia type 2 has multiple ancestral origins.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a dominant neurodegenerative disorder due to expansions of a CAG repeat tract (CAGexp) at the ATXN2 gene. Previous studies found only one ancestral haplotype worldwide, with a C allele at rs695871. This homogeneity was unexpected, given the severe anticipations related to SCA2. We aimed to describe informative ancestral haplotypes found in South American SCA2 families. METHODS: Seventy-seven SCA2 index cases were recruited from Brazil, Peru, and Uruguay; 263 normal chromosomes were used as controls. The SNPs rs9300319, rs3809274, rs695871, rs1236900 and rs593226, and the STRs D12S1329, D12S1333, D12S1672 and D12S1332, were used to reconstruct haplotypes. RESULTS: Eleven ancestral haplotypes were found in SCA2 families. The most frequent ones were A-G-C-C-C (46.7 % of families), G-C-C-C-C (24.6 %) and A-C-C-C-C (10.3 %) and their mean (sd) CAGexp were 41.68 (3.55), 40.42 (4.11) and 45.67 (9.70) (p = 0.055), respectively. In contrast, the mean (sd) CAG lengths at normal alleles grouped per haplotypes G-C-G-A-T, A-G-C-C-C and G-C-C-C-C were 22.97 (3.93), 23.85 (3.59), and 30.81 (4.27) (p < 0.001), respectively. The other SCA2 haplotypes were rare: among them, a G-C-G-A-T lineage was found, evidencing a G allele in rs695871. CONCLUSION: We identified several distinct ancestral haplotypes in SCA2 families, including an unexpected lineage with a G allele at rs695871, a variation never found in hundreds of SCA2 patients studied worldwide. SCA2 has multiple origins in South America, and more studies should be done in other regions of the world.

Chimerism 47,XY, + 8/46,XX: Follow-up for 11 Years.

Approximately 30 sex chromosome discordant chimera cases have been reported to date. In particular, there are few reported cases of chimerism involving coexisting normal and abnormal lineages that each carries a distinct sex chromosome complement. To our knowledge, this is the first case of sexual chimerism with a simultaneous chromosomal aneuploidy involving chromosome 8. This report represents the data from 11 years of follow-up.

O protocolo ASSYST-RG reduz estresse em profissionais da saúde na pandemia / The ASSYST protocol reduces stress in health care workers in the pandemic

Introdução: o aparecimento de casos de COVID-19 acarretou o surgimento de estresse agudo na população em geral, em especial nos profissionais da saúde e, dentre eles, nos de saúde mental, que passaram a ter alta demanda para atendimento a pessoas acometidas de transtornos relacionados a trauma e a estressores, em decorrência de isolamento social, internação hospitalar, óbitos, piora da situação financeira com a perda de emprego, dentre outros. Objetivo: este trabalho, realizado com o Protocolo para Estabilização da Síndrome do Estresse Agudo remoto, em formato grupal, tem por Objetivo fornecer os primeiros cuidados psicológicos, visando a reduzir as perturbações e melhorar o funcionamento adaptativo, evitando a evolução para quadros psicológicos mais disfuncionais, como o transtorno de estresse pós-traumático (TEPT). Metodologia: foram selecionados 23 participantes (psicólogos) e todos responderam às escalas de avaliação psicométrica (HADS e PCL-5) antes e depois de duas (2) sessões de terapia on-line (videoconferência), com aplicação do referido Protocolo. Resultados: o modelo de regressão mostra redução média no escore de ansiedade de -2,3 (ep 0,9), com p-valor = 0,0010 (significante); no escore de depressão, média de 1,13 (p=0,125); e no escore de TEPT, redução média de ­9,5 (3,3), com p-valor=0,006. Discussão: os Resultados estatísticos revelaram aproximação com os Resultados da pesquisa realizada por Becker et al. Assim como esses autores, nenhum efeito adverso foi relatado pelos participantes durante a intervenção, confirmando a eficácia, a viabilidade e a segurança do Assyst-RG. Conclusão: os Resultados evidenciam que o Assyst-RG foi eficaz na diminuição da ansiedade, da depressão e do TEPT.

Introduction: the emergence of cases of COVID-19 led to the emergence of acute stress in the general population, especially in health professionals and, among them, in mental health, who began to have a high demand for care for people suffering from disorders. related to trauma and stressors as a result of: social isolation, hospitalization, deaths, worsening of the financial situation with loss of job, among others. Objective: this work with the Protocol for the Stabilization of Acute Remote Stress Syndrome in Group Format aims to provide the first psychological care to reduce disturbances and improve adaptive functioning, avoiding the evolution to more dysfunctional psychological conditions such as Post Stress Disorder -Traumatic (PTSD). Methodology: twenty-three (23) participants (psychologists) were selected and all responded to psychometric assessment scales (HADS and PCL-5) before and after 2 (two) online therapy sessions (videoconference) with application of the protocol. Results: the regression model shows a mean reduction in the anxiety score of -2.3 (ep 0.9), with p-value = 0.0010; significant; in the depression score, mean of 1.13 (p=0.125); and in the PTSD score, a mean reduction of ­9.5 (3.3), with p-value=0.006. Discussion: the statistical Results revealed an approximation with the Results of the research carried out by Becker et al (2021). According to these authors, no adverse effects were reported by the participants during the intervention, confirming the efficacy, feasibility and safety of ASSYST-RG. Conclusion: the Results show that ASSYST-RG was effective in reducing anxiety, depression and PTSD.

Mutational spectrum of breast cancer susceptibility genes among women ascertained in a cancer risk clinic in Northeast Brazil.

PURPOSE: There is a paucity of data on the spectrum and prevalence of pathogenic variants among women of African ancestry in the Northeast region of Brazil. METHODS: We performed BROCA panel sequencing to identify inherited loss-of-function variants in breast cancer susceptibility genes among 292 Brazilian women referred to a single institution cancer risk assessment program. RESULTS: The study included a convenient cohort of 173 women with invasive breast cancer (cases) and 119 women who were cancer-free at the time of ascertainment. The majority of the women self-reported as African-descended (67% for cases and 90.8% for unaffected volunteers). Thirty-seven pathogenic variants were found in 36 (20.8%) patients. While the spectrum of pathogenic variants was heterogeneous, the majority (70.3%) of the pathogenic variants were detected in high-risk genes BRCA1, BRCA2, PALB2, and TP53. Pathogenic variants were also found in the ATM, BARD1, BRIP1, FAM175A, FANCM, NBN, and SLX4 genes in 6.4% of the affected women. Four recurrent pathogenic variants were detected in 11 patients of African ancestry. Only one unaffected woman had a pathogenic variant in the RAD51C gene. Different risk assessment models examined performed well in predicting risk of carrying germline loss-of-function variants in BRCA1 and/or BRCA2 in breast cancer cases. CONCLUSION: The high prevalence and heterogenous spectrum of pathogenic variants identified among self-reported African descendants in Northeast Brazil is consistent with studies in other African ancestry populations with a high burden of aggressive young onset breast cancer. It underscores the need to integrate comprehensive cancer risk assessment and genomic testing in the management of newly diagnosed Black women with breast cancer across the African Diaspora, enabling improved cancer control in admixed underserved and understudied populations.

Searching chromosome mosaicisms in 45, X Turner syndrome: how relevant is it?

ABSTRACT Objective: To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). Materials and methods: FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data. Results: Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings. Conclusions: FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.

Searching chromosome mosaicisms in 45,X Turner syndrome: how relevant is it?

OBJECTIVE: To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). METHODS: FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data. RESULTS: Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings. CONCLUSION: FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.

Is there an association between prostate-specific antigen and androgen levels in 46, XX patients with congenital adrenal hyperplasia?

INTRODUCTION: Congenital adrenal hyperplasia (CAH), a genetic disease characterized by defective cortisol synthesis and excessive levels of sex hormones, can cause precocious puberty in both sexes in untreated individuals and virilization in female patients with a 46, XX karyotype. The female paraurethral (Skene's) gland has been reported as prostate analogous. Growth of prostate tissue is associated with androgen production; therefore, prostate-specific antigen (PSA) levels may represent a marker of virilization in 46, XX patients with CAH. OBJECTIVES: To describe PSA levels in 46, XX patients and evaluate whether higher PSA levels are associated with androgenization and the severity of the disease. STUDY DESIGN: Sixty-six patients with CAH and a 46, XX karyotype were included, irrespective of age. Serum PSA, testosterone, 17-hydroxyprogesterone (17-OHP) and androstenedione levels were measured. Patients' age, age at diagnosis, forms of the disease, Prader classification, bone age assessment, sex of rearing, surgery, and the presence of clinical complications were obtained from their medical records. RESULTS: The mean age of patients was 11.45 ± 10.74 years. Forty-three patients (65%) were diagnosed neonatally at a median of 0.08 years (mean 1.47 ± 2.34 years), with registers of 17-OHP measurements (Guthrie test) being available in 51%. Testosterone, 17-OHP and androstenedione were significantly high. PSA was detectable in 25% of cases (levels >0.01 ng/ml), with a mean of 0.03 ± 0.09 ng/ml, and only in patients over five years of age. A correlation was found between PSA and age (p < 0.001), age at diagnosis (p = 0.002), testosterone (p = 0.001) and androstenedione (p = 0.023). There was no correlation between PSA and the forms of CAH or Prader classification. A sub-analysis of the patients over five years of age in whom PSA was detectable also showed that there was a correlation between PSA (p < 0.05) and age at analysis, age at diagnosis, testosterone and androstenedione levels. DISCUSSION: Limitations of this study include the small sample size due to the rareness of the disease, its retrospective nature, the absence of a control group, the fact that the sample was selected at two referral centers, which could have resulted in a selection bias, and the use of different reference values in the different laboratories conducting the PSA tests. CONCLUSIONS: PSA is detectable in 25% of 46, XX patients with CAH, only after five years of age. PSA level increases significantly with age, age at diagnosis, and testosterone and androstenedione levels, confirming a correlation between PSA levels and elevated androgen levels.

Vocal profile of 46,XX individuals with congenital adrenal hyperplasia. / Perfil vocal de indivíduos 46,XX com hiperplasia adrenal congênita.

PURPOSE: Describe the vocal profile of 46,XX congenital adrenal hyperplasia (CAH) patients followed up at the Genetics Outpatient Clinic of the Federal University Bahia (GOC-UFBA). METHODS: This is a descriptive, exploratory, cross-sectional study. The study sample consisted of 28 volunteers: 14 individuals diagnosed with CAH, followed up by the multiprofessional team of the GOC-UFBA, and 14 46,XX individuals without vocal changes and endocrine and/or genetic pathologies. Voice sample collection was performed individually in a quiet environment with participants properly seated. Acoustic (PRAAT program) and auditory-perceptual (Consensus Auditory-Perceptual Evaluation of Voice - CAPE-V) analyses were conducted. RESULTS: In the qualitative assessment of pitch, eight (61.54%) patients in the CAH group showed low vocal pattern and eight (61.54%) individuals in the group without CAH presented high vocal pattern. There were statistically significant differences between the groups only for the following vocal attributes of the CAPE-V: overall severity (p=0.01), roughness (p=0.00), and pitch (p=0.01). No statistically significant difference was observed in the other acoustic parameters investigated (p>0.05). CONCLUSION: The present study demonstrated that 46,XX CAH individuals, even when submitted to hormone therapy, present rough, low, deviant voice.

OBJETIVO: Descrever o perfil vocal de indivíduos 46,XX com hiperplasia adrenal congênita, acompanhados no Ambulatório de Genética da Universidade Federal da Bahia (UFBA). MÉTODO: Trata-se de um estudo descritivo e exploratório, com corte transversal. A amostra foi de conveniência e participaram do estudo 28 voluntários, 14 diagnosticados com hiperplasia adrenal congênita, acompanhados pela equipe multiprofissional do Ambulatório de Genética da UFBA, e 14 indivíduos 46,XX sem alterações vocais e ausência de patologia de cunho endócrino e/ou genético. A coleta das vozes foi realizada individualmente, em um ambiente silencioso, com as participantes devidamente sentadas. Realizaram-se análises perceptivo-auditiva (CAPE-V) e acústica. RESULTADOS: Em relação ao julgamento qualitativo do pitch, verificou-se que oito (61,54%) pacientes do grupo com hiperplasia adrenal congênita apresentaram um padrão vocal agravado e 8 (61,54%) do grupo sem a doença apresentaram um padrão vocal agudizado. Houve diferença estatisticamente significante entre os grupos apenas para as medidas da análise perceptivo-auditiva (CAPE-V) grau geral (p = 0,01), rugosidade (p = 0,00) e pitch (p = 0,01). Os demais parâmetros investigados na análise acústica não diferiram significativamente (p > 0,05). CONCLUSÃO: O presente estudo demonstrou que indivíduos 46,XX com hiperplasia adrenal congênita, mesmo submetidos à terapêutica hormonal, apresentam qualidade vocal rugosa, pitch agravado e voz desviada.

METABOLIC CONTROL AND BODY COMPOSITION OF CHILDREN AND ADOLESCENTS WITH PHENYLKETONURIA.

OBJECTIVE: To characterize metabolic control and verify whether it has any relation with socioeconomic, demographic, and body composition variables in children and adolescents with phenylketonuria (PKU) diagnosed in the neonatal period. METHODS: This cohort study collected retrospective data of 53 phenylketonuric children and adolescents. Data on family income, housing, and mother's age and schooling level were collected, and anthropometric measures of body composition and distribution were taken. All dosages of phenylalanine (Phe) from the last five years (2015-2019) were evaluated and classified regarding their adequacy (cutoffs: 0-12 years: 2-6 mg/dL; 12-19 years: 2-10 mg/dL). Adequate metabolic control was considered if ≥7%) of the dosages were within desired ranges. RESULTS: The mean (±standard deviation) age in the last year was 10.1±4.6 years. Most of them were under 12 years old (33/53; 62.3%) and had the classic form of the disease (39/53; 73.6%). Better metabolic control was observed among adolescents (68.4 versus 51.4%; p=0.019). Overweight was found in 9/53 (17%) and higher serum Phe levels (p<0.001) were found in this group of patients. Metabolic control with 70% or more Phe level adequacy decreased along with the arm muscle area (AMA) (ptendency=0.042), being 70.0% among those with low reserve (low AMA), and 18.5% among those with excessive reserve (high AMA). CONCLUSIONS: Adequate metabolic control was observed in most patients. The findings suggest that, in this sample, the levels of phenylalanine may be related to changes in body composition.

Metabolic control and body composition of children and adolescents with phenylketonuria / Controle metabólico e composição corporal de crianças e adolescentes com diagnóstico neonatal de fenilcetonúria

ABSTRACT Objective: To characterize metabolic control and verify whether it has any relation with socioeconomic, demographic, and body composition variables in children and adolescents with phenylketonuria (PKU) diagnosed in the neonatal period. Methods: This cohort study collected retrospective data of 53 phenylketonuric children and adolescents. Data on family income, housing, and mother's age and schooling level were collected, and anthropometric measures of body composition and distribution were taken. All dosages of phenylalanine (Phe) from the last five years (2015-2019) were evaluated and classified regarding their adequacy (cutoffs: 0-12 years: 2-6 mg/dL; 12-19 years: 2-10 mg/dL). Adequate metabolic control was considered if ≥7%) of the dosages were within desired ranges. Results: The mean (±standard deviation) age in the last year was 10.1±4.6 years. Most of them were under 12 years old (33/53; 62.3%) and had the classic form of the disease (39/53; 73.6%). Better metabolic control was observed among adolescents (68.4 versus 51.4%; p=0.019). Overweight was found in 9/53 (17%) and higher serum Phe levels (p<0.001) were found in this group of patients. Metabolic control with 70% or more Phe level adequacy decreased along with the arm muscle area (AMA) (ptendency=0.042), being 70.0% among those with low reserve (low AMA), and 18.5% among those with excessive reserve (high AMA). Conclusions: Adequate metabolic control was observed in most patients. The findings suggest that, in this sample, the levels of phenylalanine may be related to changes in body composition.

RESUMO Objetivo: Caracterizar o controle metabólico e verificar se existe relação entre ele, variáveis socioeconômicas, demográficas e composição corporal de crianças e adolescentes com fenilcetonúria (FNC) diagnosticada no período neonatal. Métodos: Coorte com coleta retrospectiva de dados de 53 crianças e adolescentes fenilcetonúricos. Foram coletados dados de renda familiar, moradia, idade e escolaridade materna e realizaram-se medidas antropométricas de composição e distribuição corporal. Todas as dosagens de fenilalanina (Fal) dos últimos cinco anos (2015-2019) foram avaliadas e classificadas quanto à adequação (cortes: 0-12 anos: 2-6 mg/dL; 12-19 anos: 2-10 mg/dL). A proporção de dosagens adequadas ≥70% foi considerada como controle metabólico adequado. Resultados: A média (±desvio padrão) de idade, no último ano, foi de 10,1±4,6 anos. A maioria tinha menos de 12 anos (33/53; 62,3%) e apresentava a forma clássica da doença (39/53; 73,6%). Observou-se melhor controle metabólico entre os adolescentes (68,4 vs. 51,4%; p=0,019). Excesso de peso foi encontrado em 9/53 (17%) e maiores níveis séricos de Fal foram descritos nesse grupo (p<0,001). O percentual de controle metabólico com 70% ou mais de adequação dos níveis de Fal foi decrescente de acordo com a área muscular do braço (AMB; ptendência=0,042), sendo de 70% entre os de baixa reserva (AMB reduzida) e de 18,5% entre os com excesso (AMB elevada). Conclusões: Observou-se controle metabólico adequado na maioria dos avaliados e os achados sugerem que, nesta amostra, os níveis de fenilalanina podem estar relacionados com alterações da composição corporal.

Perfil vocal de indivíduos 46, XX com hiperplasia adrenal congênita / Vocal profile of 46, XX individuals with congenital adrenal hyperplasia

RESUMO Objetivo Descrever o perfil vocal de indivíduos 46,XX com hiperplasia adrenal congênita, acompanhados no Ambulatório de Genética da Universidade Federal da Bahia (UFBA). Método Trata-se de um estudo descritivo e exploratório, com corte transversal. A amostra foi de conveniência e participaram do estudo 28 voluntários, 14 diagnosticados com hiperplasia adrenal congênita, acompanhados pela equipe multiprofissional do Ambulatório de Genética da UFBA, e 14 indivíduos 46,XX sem alterações vocais e ausência de patologia de cunho endócrino e/ou genético. A coleta das vozes foi realizada individualmente, em um ambiente silencioso, com as participantes devidamente sentadas. Realizaram-se análises perceptivo-auditiva (CAPE-V) e acústica. Resultados Em relação ao julgamento qualitativo do pitch, verificou-se que oito (61,54%) pacientes do grupo com hiperplasia adrenal congênita apresentaram um padrão vocal agravado e 8 (61,54%) do grupo sem a doença apresentaram um padrão vocal agudizado. Houve diferença estatisticamente significante entre os grupos apenas para as medidas da análise perceptivo-auditiva (CAPE-V) grau geral (p = 0,01), rugosidade (p = 0,00) e pitch (p = 0,01). Os demais parâmetros investigados na análise acústica não diferiram significativamente (p > 0,05). Conclusão O presente estudo demonstrou que indivíduos 46,XX com hiperplasia adrenal congênita, mesmo submetidos à terapêutica hormonal, apresentam qualidade vocal rugosa, pitch agravado e voz desviada.

ABSTRACT Purpose Describe the vocal profile of 46,XX congenital adrenal hyperplasia (CAH) patients followed up at the Genetics Outpatient Clinic of the Federal University Bahia (GOC-UFBA). Methods This is a descriptive, exploratory, cross-sectional study. The study sample consisted of 28 volunteers: 14 individuals diagnosed with CAH, followed up by the multiprofessional team of the GOC-UFBA, and 14 46,XX individuals without vocal changes and endocrine and/or genetic pathologies. Voice sample collection was performed individually in a quiet environment with participants properly seated. Acoustic (PRAAT program) and auditory-perceptual (Consensus Auditory-Perceptual Evaluation of Voice - CAPE-V) analyses were conducted. Results In the qualitative assessment of pitch, eight (61.54%) patients in the CAH group showed low vocal pattern and eight (61.54%) individuals in the group without CAH presented high vocal pattern. There were statistically significant differences between the groups only for the following vocal attributes of the CAPE-V: overall severity (p=0.01), roughness (p=0.00), and pitch (p=0.01). No statistically significant difference was observed in the other acoustic parameters investigated (p>0.05). Conclusion The present study demonstrated that 46,XX CAH individuals, even when submitted to hormone therapy, present rough, low, deviant voice.

Perfil epidemiológico de anomalias congênitas no Estado da Bahia / Epidemiological Profile of Congenital Anomalies in the State of Bahia

Objetivo: o estudo tem por objetivo apresentar dados sobre os registros de Desordens Congênitas em menores de 1 ano no Estado da Bahia entre 2012 e 2016. Metodologia: estudo epidemiológico e descritivo, com obtenção de dados secundários do Departamento de Informática do Sistema Único de Saúde (DATASUS), no período de 2012 a 2016, por meio de consulta no SIHSUS (Sistema de Informações Hospitalares do Sistema Único de Saúde), Sistema de Informações sobre Nascidos Vivos ­ SINASC, e Estatísticas Vitais do TABNET disponibilizados nesta plataforma. Resultados: foi observado um total de 7406 nascidos vivos por ocorrência de anomalias congênitas neste período, onde o maior número de casos foi registrado em 2016 (23,95%). A média de nascidos vivos com anomalias congênitas corresponde 2.468 indivíduos. As os defeitos congênitos de maior incidência se referem a malformações e deformidades congênitas do aparelho osteomuscular (48,04%). As alterações congênitas que registraram maior morbidade estavam relacionadas àquelas originadas do aparelho circulatório (26,75% de todos os casos de internação), sendo também as principais causas de óbito neste mesmo período (38,07%). Conclusão: nesta série histórica observa-se que as anomalias são as mais frequentes em nascidos vivos no período de 2012 a 2016, onde malformações congênitas do aparelho circulatório as de maior causa de morbidade e mortalidade no primeiro ano de vida. Um número de 1060 óbitos por malformações cardíacas e circulatórias em menores de 1 ano de vida foi registrado a despeito de um total de nascidos vivos de 161 indivíduos registrados nessa base de dados. Acreditamos que a divergência dessas informações possa ter ocorrido por falha na alimentação dos dados, pela forma da implantação do e pelas dificuldades quanto à interpretação e o uso do CID-10. A alimentação inadequada das informações pelo DATASUS limita a representação real dos valores para se construir um mapeamento do comportamento das malformações congênitas e suas repercussões em saúde pública.

Objective: the study aims to present data about Congenital Disorders records in children under 1 year in the State of Bahia between 2012 and 2016. Methodology: epidemiological and descriptive study, with secondary data of the Data Processing Department of the National Health System (DATASUS), in the period from 2012 to 2016, by querying the SIHSUS (Hospital Information System of the National Health System), Live Births Information System ­ SINASC, and Vital statistics of TABNET available on this platform. Results: it was observed a total of 7406 live births for occurrence of congenital anomalies in this period, where the largest number of cases was registered in 2016 (23,95%). The average number of live births with congenital anomalies corresponds to 2,468 individuals. Congenital defects of greater incidence refer to congenital deformities and malformations of the musculoskeletal system (48,04%). Congenital changes that recorded greater morbidity were related to those originating from the circulatory system (26,75% of all cases of hospitalization), also recorded as the main causes of death in this same period (38,07%). Conclusion: in this historical series it is noted that the anomalies in live births are the most frequent in the period from 2012 to 2016, where congenital malformations of circulatory system are the leading cause of morbidity and mortality in the first year of life. A number of 1060 deaths caused by cardiac and circulatory malformations in children under 1 year of life was recorded despite a total live births of 161 individuals registered in this database. We believe that the divergence of this information may have been due to failure in data feed, by means of its deployment and by the difficulties concerning the interpretation and the use of CID-10. The inadequate feed of information by the DATASUS limits the actual representation of the values to construct a behavior mapping of congenital malformations and its impact on public health.

Description of rare mutations and a novel variant in Brazilian patients with Cystic Fibrosis: a case series from a referral center in the Bahia State.

Knowledge of the genetic profile of Cystic Fibrosis (CF) contributes to a better understanding of the genotype/phenotype relationship, particularly in mixed populations such as in Brazil. To describe clinical data of CF patients with rare or not yet observed CFTR gene mutations in Brazil. It was a case series of CF patients followed-up at a referral center. Clinical and laboratory data were obtained through medical records. Molecular analysis of the mutations was performed by conventional methods and/or by next-generation sequencing. Ten patients were studied, seven had five pathogenic mutations without previous description in Brazil (Q1100P, Y109C, A107P, E1409K and K162E), one of which has not yet been reported in patients with CF (A107P). Among the seven patients, three (two siblings) had the second mutant allele of rare occurrence among Brazilians patients (G1069R and 2307insA). Three other patients also had at least one rare variant (V201M, S466X and G1069R). The age of the CF diagnosis ranged from 1 to 190 months in the ten cases and the main clinical manifestations were respiratory symptoms and difficulty in gaining weight. All but one patient presented clinical and/or laboratory data compatible with pancreatic insufficiency. The identification of rare or not yet described CFTR mutations in patients with CF in Brazil highlights the high genetic heterogeneity in this population. Knowledge of the genotypic profile of Brazilian CF patients can contribute to the development of specific mutation panels for the genetic investigation targeting each region of the country, as well as helping to understand the complex genotype/phenotype relationship, especially in mixed populations.

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.

Bisphosphonates: Pharmacokinetics, bioavailability, mechanisms of action, clinical applications in children, and effects on tooth development.

Bisphosphonates (BPs) avidly bind to calcium crystals and inhibit osteoclastic bone resorption, making them useful for treatment of skeletal disorders such as osteoporosis, Paget's disease, osteogenesis imperfecta and metastatic bone diseases. BPs therapeutically act by causing toxic effects on osteoclasts or interfering with specific intracellular pathways in those cells. BPs that possess nitrogen in their composition are called nitrogen-containing BPs (NBPs) and include alendronate, pamidronate, risedronate, ibandronate, and zoledronate. Simple BPs or non-NBPs do not have nitrogen in their composition, include etiodronate and clodronate, and were the first to be tested in animals and clinically used. Because BPs may be administered to pregnant women or children during deciduous and permanent teeth development, it is expected that they might disturb tooth eruption and development. A review of current literature on pharmacokinetics, bioavailability, mechanisms of action, and clinical applications of BPs in children, and their effects on tooth eruption and development is presented.

Clinical profile of 93 cases of 46, XY disorders of sexual development in a referral center.

The term DSD refers to disorders that affect the normal process of sexual development causing disagreement between chromosomal, gonadal and phenotypic sex, and this study aimed to describe the clinical profile of a group with DSD 46, XY joined on DSD Clinic of Hospital of Salvador, Bahia Clinics. It was a retrospective study of medical records of survey data of 93 patients with DSD 46, XY. Among the patients studied 50.5% had no defined etiology and 20.4% had androgen insensitivity syndrome (AIS), 63.4% had been initially recorded in males, 31 (33.3%) in females, being that in two it was necessary to reassignment. All patients with complete AIS pure gonadal dysgenesis and had female genitalia. Others have been diagnosed with genital ambiguity or severe hypospadias and cryptorchidism. The gonads were palpable at the first consultation in 75.3% of patients. It is important to establish an active surveillance program for these patients. The first assessment took place before the age of ten in more than 50% of cases, which shows that much needs to be done for medical education and community about the DSD. Because the phenotypic variability of sexual development disorders was noted that the clinical profile of patients studied ranged between different etiologies, including hindering the diagnostic conclusion of these individuals.

Clinical profile of 93 cases of 46, XY disorders of sexual development in a referral center

ABSTRACT The term DSD refers to disorders that affect the normal process of sexual development causing disagreement between chromosomal, gonadal and phenotypic sex, and this study aimed to describe the clinical profile of a group with DSD 46, XY joined on DSD Clinic of Hospital of Salvador, Bahia Clinics. It was a retrospective study of medical records of survey data of 93 patients with DSD 46, XY. Among the patients studied 50.5% had no defined etiology and 20.4% had androgen insensitivity syndrome (AIS), 63.4% had been initially recorded in males, 31 (33.3%) in females, being that in two it was necessary to reassignment. All patients with complete AIS pure gonadal dysgenesis and had female genitalia. Others have been diagnosed with genital ambiguity or severe hypospadias and cryptorchidism. The gonads were palpable at the first consultation in 75.3% of patients. It is important to establish an active surveillance program for these patients. The first assessment took place before the age of ten in more than 50% of cases, which shows that much needs to be done for medical education and community about the DSD. Because the phenotypic variability of sexual development disorders was noted that the clinical profile of patients studied ranged between different etiologies, including hindering the diagnostic conclusion of these individuals.

Spinocerebellar ataxias in Brazil--frequencies and modulating effects of related genes.

This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6 %), 28 SCA2 (7.8 %), 20 SCA7 (5.6 %), 15 SCA1 (4.2 %), 12 SCA10 (3.3 %), 5 SCA6 (1.4 %), and 65 families without a molecular diagnosis (18.1 %). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7 % of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset (p < 0.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented.