Lilia Maria de Azevedo Moreira

Objetivo: trazer conhecimentos sobre a hereditariedade do albinismo em famílias da Bahia, estado com estimativa de taxa elevada da característica. Métodos: pesquisa seccional descritiva por amostragem de conveniência, com consulta às fichas de atendimento do programa Genética e Sociedade (Instituto de Biologia- UFBA) e ao banco de dados da Associação de Pessoas com Albinismo da Bahia (APALBA). Resultados: no total de 457 albinos, verificaram-se 265 com mais de um caso de albinismo na família (58%). Casais formados por pessoas albinas tiveram filhos com a mesma característica, o que concorda com o modelo clássico de herança autossômica recessiva para o albinismo, que preconiza nesta situação 100% dos filhos também albinos. Entretanto, em uma família, o casal albino com traços fenotípicos de diferentes subtipos teve um filho pigmentado com avaliação oftalmológica normal. Essa ocorrência foi associada à heterogeneidade genética do albinismo parental. Conclusões: estudos sobre a transmissão hereditária do albinismo em populações numerosas podem trazer contribuições para escolhas reprodutivas, aconselhamento genético e acompanhamento em saúde, tendo em vista a implantação precoce de medidas preventivas de danos à pele e à visão.

Taxa elevada de albinismo oculocutâneo no estado da Bahia, região nordeste do Brasil

Individuals with ring chromosome 13 may show characteristics observed in a deletion syndrome and could present a set of dismorphies along with intellectual disability, according to chromosomal segments involved in the genetic imbalance. Nevertheless, ring anomalies likewise is called “dynamic mosaicism”, phenomena triggered by the inner instability concerning the ring structure, thus leading to the establishment of different cell clones with secondary aberrations. Phenotypic features, such as growth failure and other anomalies in patients with this condition have been associated with an inherent ring chromosome mitotic instability, while recent studies offer evidence on a role played by the differential loss of genes implicated in development. Here, we observed similar mosaicism rates and specific gene loss profile among three individuals with ring chromosome 13 using GTW‐banding karyotype analyses along with FISH and CGH‐array approaches. Karyotypes results were: patient 1—r(13)(p13q32.3), patient 2—r(13)(p11q33.3), and patient 3—r(13)(p12q31.1). Array‐CGH has revealed qualitative genetic differences among patients in this study and it was elusive in precise chromosomal loss statement, ranging from 13 Mb, 6.8 Mb, and 30 Mb in size. MIR17HG and ZIC2 loss was observed in a patient with digital anomalies, severe growth failure, microcephaly and corpus callosum agenesis while hemizygotic EFNB2 gene loss was identified in two patients, one of them with microphtalmia. According to these findings, it can be concluded that specific hemizygotic loss of genes related to development, more than dynamic mosaicism, may be causative of congenital anomalies shown in patients with ring 13 chromosome.

Objective: To describe genetic aspects and characteristics associated with premature aging in adults with Down syndrome. Method: A cross-sectional study was carried out of 28 individuals with Down syndrome, aged between 20 and 54 years old (13 women and 15 men), in a university community genetics program, who were referred by philanthropic institutions which offers support to people with disabilities and their families. The genetic and functional data were recorded in anamnesis forms. Results: Karyotype analysis revealed free trisomy 21, with only one hereditary case of translocation between chromosomes 15/21. In the sample group, functional difficulties were observed in locomotion, sedentary lifestyles, behavior disorders, memory loss and depression symptoms, as well as loss of autonomy at more advanced ages. Only three people had reading and writing skills and 16 had good social relationships and friend-making skills. Conclusion: The study confirms that premature aging in Down syndrome starts in adulthood, and therapeutic follow-up is recommended with the implementation of interventions to prevent deficits and stimulate cognition, and activities for quality of life.

Introdução: a doença de Huntington (DH) é uma enfermidade neurodegenerativa e de desenvolvimento tardio, autossômica dominante. Declínio cognitivo, coréia, disfunção motora severa e óbito no estágio final, são sintomas que caracterizam a doença. Atualmente, testes moleculares para diagnóstico pré-sintomático estão acessíveis à população em risco, porém implicações éticas permeiam esse tipo de exames. Objetivo: avaliar aspectos atuais da realização de testes genéticos para DH no Brasil por meio de estudo analítico de amostra de laboratórios. Metodologia: foram utilizados questionários semiestruturados enviados a 19 laboratórios que ofereciam testes diagnósticos e preditivos para a doença em suas paginas virtuais, por meio de correio eletrônico, a fim de obter informações sobre a metodologia empregada para os testes, infraestrutura, composição da equipe técnica, sexo dos indivíduos atendidos, percentagem de resultados positivos e cuidados oferecidos ao indivíduo/família antes e após a realização dos exames. Resultados: os laboratórios que aceitaram participar do estudo e responderam ao questionário informaram dispor de uma infraestrutura excelente, em termos de pessoal e equipamentos, atendendo aos requisitos básicos para a realização dos exames utilizando principalmente a técnica da Reação em Cadeia da Polimerase (PCR), na metodologia molecular. O percentual de resultado positivo para DH nos laboratórios pesquisados variou de 30 a 90%, sendo que este último percentual foi apresentado pelo laboratório vinculado a Instituto Público de Ensino Superior que era o único a oferecer acompanhamento psicológico e/ou psiquiátrico antes e após os exames. Conclusão: para promover a ampliação do acesso a esse tipo de teste à população acometida pela doença de Huntington, deve ser estimulada a criação de laboratórios com tecnologia de ponta e a formação de recursos humanos especializados.

Few patients with interstitial deletions in the distal long arm of chromosome 14 have been reported, and these patients showed rather indistinct features, including growth and mental retardation and phenotypic alterations. We describe a de novo 14q interstitial deletion in a 6-year-old boy with dysmorphic facial traits such as hypertelorism, short and narrow palpebral fissures, broad nose with anteverted nostrils, long philtrum, thin upper lip with cupid’s bow, prominent and everted lower lip, mildly low-set ears, as well as moderate developmental delay and mild mental retardation. Array-CGH mapped the deletion to the region 14q24.3 to 14q31.3, including 13.11 Mb, proximal to the imprinted genomic region of 14q32. This mild phenotypic presentation suggests that the deleted segment does not contain essential genes for early organ development. Twenty-two genes with known functions, including Neurexin III (NRXN3, OMIM 600567), map to the region deleted in the propositus.

Objectives: Congenital adrenal hyperplasia (CAH) is a disease that occurs during fetal development and can lead to virilization in females or death in newborn males if not discovered early in life. Because of this there is a need to seek morphological markers in order to help diagnose the disease. In order to test the hypothesis that prenatal hormones can affect the sexual dimorphic pattern 2D:4D digit ratio in individual with CAH, the aim of this study was to compare the digit ratio in female and male patients with CAH and control subjects.Methods: The 2D:4D ratios in both hands of 40 patients (31 females—46, XX, and 9 males—46, XY) were compared with the measures of control individuals without CAH (100 males and 100 females).Results: Females with CAH showed 2D:4D ratios typical of male controls (0.950 and 0.947) in both hands (P < 0.001). In CAH males the left hand 2D:4D ratio (0.983) was statistically different from that of male controls (P < 0.05).Conclusions: These finding support the idea that sexual dimorphism in skeletal development in early fetal life is associated with differences between the exposure to androgens in males and females, and significant differences associated with adrenal hyperplasia. Although the effects of prenatal androgens on skeletal developmental are supported by numerous studies, further investigation is yet required to clarify the disease and establish the digit ratio as a biomarker for CAH. Am. J. Hum. Biol. 26:559–561, 2014.

O estudo de distúrbios cromossômicos em serviços públicos de genética pode constituir uma nova abordagem na Genética Comunitária. Tendo em vista o objetivo de avaliar a importância de estudos dessa natureza para o diagnóstico e o encaminhamento precoce a tratamentos especializados, foi analisada a frequência de alterações cromossômicas em indivíduos que realizaram o cariótipo em serviço universitário de genética. Para tanto, foi feito um estudo retrospectivo de 813 casos atendidos no período de 1990 a 2010 no serviço referido. As preparações foram obtidas por cultura convencional de linfócitos e bandamento GTG nos casos com suspeita de cromossomopatia. Ocorreram alterações cromossômicas em 268 cariótipos, 32,9% dos casos estudados. A distribuição dos distúrbios esteve de acordo com estudos semelhantes realizados em diferentes centros, sendo as alterações numéricas as mais frequentes. Os resultados obtidos evidenciam a importância da citogenética no esclarecimento do diagnóstico de diferentes distúrbios congênitos, responsáveis por importante parcela da morbi-mortalidade infantil e mostra a contribuição dessa especialidade no fortalecimento da Genética Comunitária como uma nova abordagem da genética em benefício da população.

BACKGROUND: This report describes the sixth case of an unusual association: Down syndrome with achondroplasia. It also analyzes the effects of both of these disorders on patient phenotype.METHODS: A male infant was evaluated for Down syndrome. His appearance also suggested a diagnosis of achondroplasia. The child was evaluated by physical examination, radiography, cytogenetic study, and mutation analysis.RESULTS: Chromosome analysis showed a karyotype of 47,XY,+21 in all 30 cells analyzed. Radiographic examination showed typical findings of achondroplasia, such as disproportionately large skull, shortening of limb segments, and lumbar lordosis. FGFR3 screening showed a heterozygous G1138A mutation.CONCLUSIONS: The interaction of these two distinct genetic disorders in the same patient produces a phenotype typical of each syndrome with some overlapping signs. This case represents de novo origin of two disorders that both may be parental‐age related. Birth Defects Research (Part A) 2010.

Rieger syndrome (RS; OMIM 180500) is a rare autosomal dominant disorder of morphogenesis, with ocular and systemic abnormalities and variability in phenotypic expression. Some patients with RS presented with a deletion of the band 4q25 to which the homeobox gene PIT X2 (former RIEG) was mapped. To study the natural history and perform a genotype–phenotype correlation, we followed a girl with RS from the age of 1 year to puberty. The study included physical examination, clinical and psychological evaluation, and cytogenetic analysis with GTG‐banded karyotype and array CGH. Additionally, molecular analysis using microsatellite markers for chromosome 4 (D4S427, D4S194 and D4S1615) was performed. Conventional chromosome analysis showed a 4q deletion, and aCGH confirmed the determination of the breakpoints at 4q25 and 4q31. With the exception of the typical features of RS is the patient, the clinical manifestations were relatively mild, despite the relatively large size of the deleted chromosome segment. The patient was periodically re‐evaluated for several years. The teeth are still abnormal, and she is still under orthodontic treatment. The facial features were attenuated with age. Currently, she is under constant monitoring of eye pressure. She benefited from early intervention program, and her tonus is normal. She attends a normal school with minor learning difficulties. In conclusion, this study offers a comprehensive phenotypic delineation of RS through almost two decades and may contribute to a more accurate genetic counseling in cases of this syndrome.