Congenital chromoanagenesis in the routine postnatal chromosomal microarray analyses.

Chromosomal microarray analyses (CMA) have greatly increased both the yield and diagnostic accuracy of postnatal analysis; it has been used as a first-tier cytogenetic test in patients with intellectual disability, autism spectrum disorder, and multiple congenital abnormalities. During the last 15 years, we performed CMA in approximately 8,000 patients with neurodevelopmental and/or congenital disorders, of which 13 (0.16%) genetically catastrophic complex chromosomal rearrangements were identified. These ultrarare rearrangements showed clustering of breakpoints, characteristic of chromoanagenesis events. Al1 13 complex events display underlying formation mechanisms, originating either by a synchronization of the shattering of clustered chromosome regions in which regional asynchrony of DNA replication may be one of the main causes of disruption. We provide an overview of the copy number profiling in these patients. Although several previous studies have suggested that chromoanagenesis is often a genetic disease source in postnatal diagnostic screening, due to either the challenge of clinical interpretation of these complex rearrangements or the limitation of microarray resolution relative to the small size and complexity of chromogenic induced chromosome abnormalities, bringing further attention and to study its occurrence in the clinical setting is extremely important.

Leigh syndrome in a patient with a novel C12orf65 pathogenic variant: case report and literature review.

Leigh syndrome is an early onset progressive disorder caused by defects in mitochondrial oxidative phosphorylation. Pathogenic variants in nuclear and mitochondrial genes are associated with the syndrome. Homozygous pathogenic variants in the C12orf65 gene impair the mitochondrial oxidative phosphorylation system. We describe a new case of Leigh syndrome caused by a novel pathogenic variant of the C12orf65 gene resulting in the lack of the Gly-Gly-Gln (GGQ) domain in the predicted protein, and review clinical and molecular data from previously reported patients. Our study supports that the phenotype caused by C12orf65 gene variants is heterogeneous and varies from spastic paraparesis to Leigh syndrome. Loss-of-function variants are more likely to cause the disease, and variants affecting the GGQ domain tend to be associated with more severe phenotypes, reinforcing a possible genotype-phenotype correlation.

A Novel MGP Gene Mutation Causing Keutel Syndrome in a Brazilian Patient.

Keutel syndrome is caused by mutations in the matrix gamma-carboxyglutamic acid (MGP) gene (OMIM 154870) and is inherited in an autosomal recessive fashion. It is characterized by brachydactyly, pulmonary artery stenosis, a distinctive facial phenotype, and cartilage calcification. To date, only 36 cases have been reported worldwide. We describe clinical and molecular findings of the first Brazilian patient with Keutel syndrome. Keutel syndrome was suspected based on clinical and morphological evaluation, so we sequenced the MGP gene using the TruSight One Sequencing Panel (Illumina). The obtained MGP gene sequence was then validated by Sanger sequencing. We identified a novel pathogenic homozygous variant of the MGP gene (c.2T>C; p.Met1Thr) confirming Keutel syndrome. Proper diagnosis of this syndrome is important for clinical management and is an indication for genetic counseling. Keutel syndrome should be suspected in patients with cartilage calcifications and brachydactyly when associated with a distinctive facial phenotype and pulmonary artery stenosis.

Correlaçäo entre as expressöes de P-caderina e de receptores de estrógeno no câncer da mama / Correlation between P-cadherin and estrogen receptor expression in breast cancer

Introduçäo: A manutençäo da arquitetura dos tecidos adultos depende essencialmente da integridade estrutural e funcional das caderinas, uma superfamília de moléculas de adesäo celular dependentes de cálcio, que medeiam normalmente a adesäo intercelular homofílica e homotípica. A P-caderina é expressa pelas células mioepiteliais da glândula mamária normal, sendo aberrantemente expressa num pequeno subgrupo de carcinomas da mama. Vários estudos recentes têm demonstrado que a expressäo desta proteína está significativamente correlacionada com tumores de alto grau histológico e negativos para os receptores de estrógeno (RE). Objetivos: Investigar a expressäo da P-caderina e dos receptores de estrógeno (RE) em carcinomas da mama invasivos e correlacionar os resultados obtidos. Material e método: O padräo de expressäo da P-caderina e dos RE foi estudado imunoistoquimicamente em 149 carcinomas invasivos da mama; seguidamente, correlacionou-se estatisticamente a expressäo destas duas proteínas. Resultados: A P-caderina foi detectada nas células mioepiteliais do tecido mamário normal e em 46 de 146 (31,5 por cento) casos de carcinoma invasivo da mama. A expressäo da P-caderina correlacionou-se inversamente com a expressäo dos RE, verificando-se que o subgrupo de tumores P-caderina positivos e RE negativos apresentava alto grau histológico e maior agressividade tumoral. Conclusäo: Demonstrou-se que a P-caderina identifica um subgrupo de carcinomas da mama, que näo expressa RE e que parece representar um estado mais avançado da progressäo tumoral. Estes resultados levantam ainda a hipótese de que a expressäo desta proteína possa ser regulada por uma via alternativa, independente de estrógeno

Carcinoma bronquílo-alveolar associado à malformaçäo adenomatóide cística de tipo I: relato de caso e revisäo de literatura / Bronchioalveolar carcinoma complicating type I congenital cystic adenomatoid malformation: case report and review of literature

Paciente masculino de 36 anos, com cisto uniloculado no pulmäo direito, revestido por epitélio cilíndrico ciliado com atipias reativas e focos de metaplasia mucinosa. No tecido pulmonar adjacente, observou-se proliferaçäo epitelial mucossecretora focal nos septos alveolares, com discreta atipia nuclear. Estabeleceu-se o diagnóstico de carcinoma bronquíolo-alveolar mucinoso associado à malformaçäo adenomatóide cística congênita de tipo I. A provável disseminaçäo aerógena e o caráter multicêntrico desta neoplasia reforçam a importância da ressecçäo precoce das lesöes. Lobectomia complementar detectou a presença de dois outros focos de carcinoma no tecido pulmonar contíguo

Invasive medullary thymoma associated with myasthenia gravis: an unusual case

Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome