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Precise breakpoint mapping of balanced chromosomal rearrangements is crucial to identify disease etiology. Ten female patients with X-autosome balanced translocations associated with phenotypic alterations were evaluated, by mapping and sequencing their breakpoints. The rearrangements’ impact on the expression of disrupted genes, and inferred mechanisms of formation in each case were assessed. For four patients that presented one of the chromosomal breaks in heterochromatic and highly repetitive segments, we combined cytogenomic methods and short-read sequencing to characterize, at nucleotide resolution, breakpoints that occurred in reference genome gaps. Most of rearrangements were possibly formed by non-homologous end joining and have breakpoints at repeat elements. Seven genes were found to be disrupted in six patients. Six of the affected genes showed altered expression, and the functional impairment of three of them were considered pathogenic. One gene disruption was considered potentially pathogenic, and three had uncertain clinical significance. Four patients presented no gene disruptions, suggesting other pathogenic mechanisms. Four genes were considered potentially affected by position effect and the expression abrogation of one of them was confirmed. This study emphasizes the importance of breakpoint-junction characterization at nucleotide resolution in balanced rearrangements to reveal genetic mechanisms associated with the patients’ phenotypes, mechanisms of formation that originated the rearrangements, and genomic nature of disrupted DNA sequences.

Background Oculo‐auriculo‐vertebral spectrum (OAVS) is a craniofacial developmental disorder that affects structures derived from the first and second pharyngeal arches. The clinically heterogeneous phenotype involves mandibular, oral, and ear development anomalies. Etiology is complex and poorly understood. Genetic factors have been associated, evidenced by chromosomal abnormalities affecting different genomic regions and genes. However, known pathogenic single‐nucleotide variants (SNVs) have only been identified in MYT1 in a restricted number of patients. Therefore, investigations of SNVs on candidate genes may reveal other pathogenic mechanisms. Methods In a cohort of 73 patients, coding and untranslated regions (UTR) of 10 candidate genes (CRKL, YPEL1, MAPK1, NKX3‐2, HMX1, MYT1, OTX2, GSC, PUF60, HOXA2) were sequenced. Rare SNVs were selected and in silico predictions were performed to ascertain pathogenicity. Likely pathogenic variants were validated by Sanger sequencing and heritability was assessed when possible. Results Four likely pathogenic variants in heterozygous state were identified in different patients. Two SNVs were located in the 5’UTR of YPEL1; one in the 3’UTR of CRKL and one in the 3’UTR of OTX2. Conclusion Our work described variants in candidate genes for OAVS and supported the genetic heterogeneity of the spectrum. Coding and UTR of 10 candidate genes to the oculo‐auriculo‐vertebral spectrum were sequenced. Four rare SNVs, in four different patients, were considered as likely pathogenic. These findings support the genetic heterogeneity of the spectrum.

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by hemifacial microsomia associated with ear, eyes and vertebrae malformations showing highly variable expressivity. Recently, MYT1, encoding the myelin transcription factor 1, was reported as the first gene involved in OAVS, within the retinoic acid (RA) pathway. Fifty-seven OAVS patients originating from Brazil were screened for MYT1 variants. A novel de novo missense variant affecting function, c.323C>T (p.(Ser108Leu)), was identified in MYT1, in a patient presenting with a severe form of OAVS. Functional studies showed that MYT1 overexpression downregulated all RA receptors genes (RARA, RARB, RARG), involved in RA-mediated transcription, whereas no effect was observed on CYP26A1 expression, the major enzyme involved in RA degradation, Moreover, MYT1 variants impacted significantly the expression of these genes, further supporting their pathogenicity. In conclusion, a third variant affecting function in MYT1 was identified as a cause of OAVS. Furthermore, we confirmed MYT1 connection to RA signaling pathway.

The oculo-auriculo-vertebral spectrum (OAVS) is defined as a group of malformations involving the ears, mouth, mandible, eyes, and cervical spine. Establishing an accurate clinical diagnosis of OAVS is a challenge for clinical geneticists, not only because these patients display heterogeneous phenotypes, but also because its etiology encompasses environmental factors, unknown genetic factors and different chromosome aberrations. To date, several chromosomal abnormalities have been associated with the syndrome, most frequently involving chromosome 22. In the literature, six 22q11.2 microdeletions have been described within the same region, suggesting possible OAVS candidate genes in this segment. Here, we report on a patient with an ∼581-kb 22q11.21 deletion, detected by genomic array and MLPA. This is the 7th case described with OAVS and 22q deletion, suggesting that the 22q11.2 region may be related to the regulation of body symmetry and facial development.

The aim of this study was to evaluate the changes in the lipid profile, especially in conjugated linoleic acid (CLA), in 12 cream cheese batches with different prebiotic (inulin) and probiotic ( Bifidobacterium animalis and Lactobacillus acidophilus ) concentrations stored for 45 days at 8 ± 0.5 °C and analyzed every 15 days. A Central Rotational Composite Design was used to establish the prebiotic and probiotic concentrations. The effect of the pre- and probiotic concentrations on CLA contents (mg g −1 of fat) was verified by plotting the response surface. The linear, quadratic, and interaction coefficients of the multiple linear regression for both prebiotic and probiotics were not significant ( p  > 0.05). No significant changes were observed neither in the lipid profile nor in the CLA content among the different batches, in which fatty acid composition and CLA concentrations were similar to the milk used in the preparation of the cream cheese and also to the control batch.

The relationships between fungal growth and ergosterol content and between aflatoxins B1 and B2 production and ergosterol content were verified in corn grains. In the first experiment, fungal growth and ergosterol content were monitored during incubation of corn grains presenting water activities of 0.85a w and 0.92a w at 25ºC over a period of 18 days. For the Taiúba variety, the fungi growth and ergosterol content increased more rapidly for 0.92a w than 0.85a w. Maximum ergosterol levels were 2.8 and 4.6 µg/g, respectively, for 0.85a w and 0.92a w. For the Cargill hybrid 606, a more pronounced increase in fungal growth was verified just at the end of the incubation period, mainly for 0.92a w when an acentuated increase in ergosterol content was also observed. Maximum ergosterol levels detected were 1.6 µg/g and 5.8 µg/g, respectively, for 0.85a w and 0.92a w. There was a significant correlation between ergosterol content and log of CFU g-1 for 0.92a w but not for 0.85 a w. In the second experiment, samples of corn grains of the Taiúba variety at 0.87a w and 0.95a w were inoculated with a toxigenic Aspergillus flavus strain and incubated at 25ºC. Ergosterol levels reached maximum values of 12.1 and 73.4 µg/g, respectively, for 0.87a w and 0.95a w. In both water activities, content aflatoxin B1 followed the same trend as ergosterol. For the aflatoxin B2 this trend was not observed. Ergosterol assay appears to be a useful test to measure fungal growth and to indicate the possibility of aflatoxin production in corn grains. A relação entre o crescimento fúngico e o teor de ergosterol e entre a produção de aflatoxinas B1 e B2 e o teor de ergosterol foi verificada em milho em grãos. No primeiro experimento, o crescimento fúngico e o conteúdo de ergosterol foram monitorados durante incubação das amostras de milho com 0,85 e 0,92 de atividade de água (Aa) a 25ºC por um período de 18 dias. Para a variedade Taiúba o crescimento fúngico e o conteúdo de ergosterol aumentaram mais rapidamente a 0,92 de Aa do que a 0,85 de Aa. Os níveis máximos de ergosterol atingidos foram 2,8 e 4,6 µg/g, respectivamente, para 0,85 e 0,92 de Aa. Para o híbrido Cargill 606, um crescimento fúngico mais pronunciado foi verificado somente ao final do período de incubação principalmente na Aa de 0,92, quando também verificou-se um acentuado aumento do teor de ergosterol. Os níveis máximos de ergosterol detectados foram 1,6 µg/g e 5,8 µg/g, respectivamente, para as Aa de 0,85 e 0,92. Para as duas amostras verificou-se uma correlação positiva nos dois meios de cultura utilizados entre o conteúdo de ergosterol e a contagem total de unidades formadoras de colonias (UFC) g-1 de grãos na Aa de 0,92 mas não na de 0,85. No 2º experimento, amostras de milho da variedade Taiúba com 0,87 e 0,95 de Aa foram inoculadas com uma cepa toxigênica de Aspergillus flavus e incubadas a 25ºC. Os níveis de ergosterol alcançaram valores máximos de 12,1 e 73,4 µg/g, respectivamente, para as Aa de 0,87 e 0,95. Em ambas Aa testadas, a produção de aflatoxinas e o teor de ergosterol apresentaram as mesmas tendências, ou seja, o aumento nos níveis de ergosterol foi acompanhado pelo aumento na produção da aflatoxina B1. Para a aflatoxina B2 essa tendência não foi observada.