Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

An exploratory data analysis on genetic architecture in <i>Bos taurus</i> through miRNAs within QTLs and their target genes

Understanding the genetic architecture is important because it allows us to understand the relationship between molecular markers, like miRNAs, QTLs and SNPs, and traits of interest such as milk yield, lipidic content in milk, heat tolerance etc. In the present study we performed an exploratory analysis that found an association of 480 miRNAs within QTLs related to 155 traits. We also discovered that those 480 miRNAs might modulate the expression of 12.374 genes. The most predominant traits available in the data were milk related, such as milk yield and fatty acids content in milk. Besides, the functional enrichment analysis revealed that some of those genes were linked to sensory perception, olfactory perception, perception of stimulus and chemical stimulus, localization, establishment of localization, transport etc. Furthermore, the discovery of miRNAs within QTLs and their target analysis suggests that they might be associated with characteristics of interest. By analyzing these relationships, we strongly encourage that future QTL studies should include miRNAs analysis. Altogether, our analysis enabled us to explore the association between multiple complex traits, miRNAs within QTLs and their target genes in Bos taurus that might have implications in breeding programs. </p

Transcriptome Analysis Identifies Candidate Target Genes Involved in Glyphosate-Resistance Mechanism in Lolium multiflorum

Italian ryegrass (Lolium multiflorum; LOLMU) is one of the most troublesome weeds in temperate regions in the world. This weed species interfere with wheat, corn, rye, and oat, causing significant crop yield losses. This species has evolved glyphosate resistance, making it difficult to control. The mechanisms of glyphosate resistance are still unknown, and an understanding thereof will favor the development of new strategies of management. The present study is the first transcriptome study in LOLMU using glyphosate-resistant and -sensitive biotypes, aiming to identify and to provide a list of the candidate target genes related to glyphosate resistance mechanism. The transcriptome was assembled de novo, producing 87,433 contigs with an N50 of 740 bp and an average length of 575 bp. There were 92 and 54 up- and down-regulated genes, respectively, in the resistant biotype, while a total of 1683 were differentially expressed in the sensitive biotype in response to glyphosate treatment. We selected 14 highly induced genes and seven with repressed expression in the resistant biotype in response to glyphosate. Of these genes, a significant proportion were related to the plasma membrane, indicating that there is a barrier making it difficult for glyphosate to enter the cell

Comparative genomic analysis of Brazilian Leptospira kirschneri serogroup Pomona serovar Mozdok

Leptospira kirschneri is one of the pathogenic species of the Leptospira genus. Human and animal infection from L. kirschneri gained further attention over the last few decades. Here we present the isolation and characterisation of Brazilian L. kirschneri serogroup Pomona serovar Mozdok strain M36/05 and the comparative genomic analysis with Brazilian human strain 61H. The M36/05 strain caused pulmonary hemorrhagic lesions in the hamster model, showing high virulence. The studied genomes presented high symmetrical identity and the in silico multilocus sequence typing analysis resulted in a new allelic profile (ST101) that so far has only been associated with the Brazilian L. kirschneri serogroup Pomona serovar Mozdok strains. Considering the environmental conditions and high genomic similarity observed between strains, we suggest the existence of a Brazilian L. kirschneri serogroup Pomona serovar Mozdok lineage that could represent a high public health risk; further studies are necessary to confirm the lineage significance and distribution

Comparative genomics of pathogenic Leptospira interrogans serovar Canicola isolated from swine and human in Brazil

Leptospira interrogans serovar Canicola is one of the most important pathogenic serovars for the maintenance of urban leptospirosis. Even though it is considered highly adapted to dogs, serovar Canicola infection has already been described in other animals and even a few human cases. Here, we present the genomic characterisation of two Brazilian L. interrogans serovar Canicola strains isolated from slaughtered sows (L0-3 and L0-4) and their comparison with human strain Fiocruz LV133. It was observed that the porcine serovar Canicola strains present the genetic machinery to cause human infection and, therefore, represent a higher risk to public health. Both human and porcine serovar Canicola isolates also presented sequences with high identity to the Chinese serovar Canicola published plasmids pGui1 and pGui2. The plasmids identification in the Brazilian and Chinese serovar Canicola strains suggest that extra-chromosomal elements are one more feature of this serovar that was previously unnoticed

Comparative genomics of pathogenic Leptospira interrogans serovar Canicola isolated from swine and human in Brazil

<div><p>Leptospira interrogans serovar Canicola is one of the most important pathogenic serovars for the maintenance of urban leptospirosis. Even though it is considered highly adapted to dogs, serovar Canicola infection has already been described in other animals and even a few human cases. Here, we present the genomic characterisation of two Brazilian L. interrogans serovar Canicola strains isolated from slaughtered sows (L0-3 and L0-4) and their comparison with human strain Fiocruz LV133. It was observed that the porcine serovar Canicola strains present the genetic machinery to cause human infection and, therefore, represent a higher risk to public health. Both human and porcine serovar Canicola isolates also presented sequences with high identity to the Chinese serovar Canicola published plasmids pGui1 and pGui2. The plasmids identification in the Brazilian and Chinese serovar Canicola strains suggest that extra-chromosomal elements are one more feature of this serovar that was previously unnoticed.</p></div

Genomic characterisation of Leptospira inadai serogroup Lyme isolated from captured rat in Brazil and comparative analysis with human reference strain

<div><p>Leptospira inadai is classified as a species of the Leptospira intermediate group that has been poorly studied due to its apparent insignificance to human and animal health. Nevertheless, over the last two decades the species has been described in human cases in India and in carrier animals in Ecuador. Here, we present the first identification and genomic characterisation of L. inadai serogroup Lyme isolated from captured rodent in Brazil. Even though the M34/99 strain was not pathogenic for hamsters, it was able to establish renal colonisation. The M34/99 strain presented high similarity with L. inadai serogroup Lyme human reference indicating that animal strain could also infect humans, although it does not represent high risk of severe disease. An extrachromosomal sequence was also identified in M34/99 strain and presented high identity with previously described L. inadai phage LinZ_10, suggesting that phage-like extrachromosomal sequence may be another feature of this understudied species.</p></div