Digest: the role of linkage in mimicking "magic traits"

Can divergence in a mating trait increase local adaption by increasing ecological divergence? Servedio and Bürger propose that "pseudomagic traits," tightly linked complexes consisting of an ecological locus under divergent selection and a locus acting as a mating cue, can effectively mimic pleiotropy. Such pseudomagic traits can form even when linkage between ecological and mating loci is limited

89 Simultaneous ocurrence of hammock mitral valve and no-compaction cardiomyopathy

Abstract We report a 62-year-old man with a past medical history of dyslipidemia, paranoid schizophrenia and permanent atrial fibrillation. A ATTE performed at his district hospital revealed rheumatic mitral valve disease with double lesion: severe regurgitation and mild stenosis, plus moderate tricuspid regurgitation and a mean PAP of 32mm Hg. Cardiac catheterization showed no abnormalities of the coronary arteries. He was transferred to our hospital and scheduled for mitral valve replacement and tricuspid ring valvuloplasty. Preoperative transesophageal echocardiography showed an abnormal subvalvular mitral apparatus, with false tendons and multiple papillary muscles, resembling a hammock mitral valve. Most cordae tendinae arose from a single dominant papillary muscle at a posterior medial region, which provoke severe mitral regurgitation due to coaptation defect and mild subvalvular mitral stenosis. It could also be appreciated hypertrabeculation in the lateral medial, basal and apical segments. This suggested no-compaction cardiomyopathy associated with hammock mitral valve. Left ventricular systolic function was preserved. No evidence of rheumatic mitral valve disease was found in transesophageal echocardiographic study performed at our hospital. On the 30th April 2019 he underwent mechanic mitral valve replacement (Bicarbon 29mm) and tricuspid ring valvuloplasty (Edwards Physio 32mm) surgery. Once the patient was weaned from cardiopulmonary bypass, severe left ventricle systolic dysfunction ensued, predominantly localized in the anterior, inferior septal, inferior lateral basal and medial segments. Apical segments had preserved mobility An adrenalin infusion prior weaning from CBP was initiated. Preserved mobility of the mitral prosthesis discs was observed. The patient developed cardiogenic shock in spite of high doses of dobutamin and adrenaline infused. IACB was implanted with 1:1 assistance. The patient was transfered to the hemodynamic room in order to rule out coronary complications. Cardiac catheterization showed no significant angiographic lesions. During the first postoperative hours, the patient was stabilized allowing progressive lowering of the drugs (adrenaline, dobutamine). TTE showed normally functioning prosthetic mitral valve and preserved left ventricle systolic function. An MRI was performed demostrating no-compaction cardiomyopathy Conclusion This case report describes a rare presentation of simultaneous ocurrence of hammock mitral valve and no-compaction cardiomyopathy. Perioperative left ventricle dysfunction in no-compaction cardiomyopathy is related to subendocardial ischemia caused during extracorporeal circulation in the multiple prominent ventricular trabeculations with deep intertrabecular recesses corresponding to non-compacted myocardium .This must be taken account in those patients with no-compaction cardiomyopathy scheduled for cardiac surgery in order to take preventive measures. Abstract 89 Figure. non - compacted myocardium </jats:sec

481 Mass compromising left atrium

Abstract A 47-year-old woman presented to the ER with a sudden-onset left side chest pain of less than one hour in duration that started at rest. The pain was severe and radiated to the left shoulder. This was accompanied with symptoms of shortness of breath and sweating but no similar episodes in the past. There was no significant history of coronary artery disease or any other illness in the family. She had dyslipidemia and a smoking habit of 1 pack/day for the previous 10years. In the ERt, she was hemodynamically stable and her physical examination was within normal limits. ECG showed ST-segment elevation in the inferior leads. No prior ECG was available for comparison. She underwent emergent PCI which showed spontaneous proximal segment circumflex (dominant) artery dissection with TIMI angiographic flow grade 0. All other coronaries were patent with TIMI III flow and no atherosclerotic changes. PCI was carried out, but unfortunately, it was complicated with coronary rupture having to implant a drug eluting stent in order to seal the vessel rupture, with optimal final result (TIMI 3). An urgent TTE was performed for evaluation of the patient due to persistence of chest pain after coronariography, revealing an echogenic mass at the left atrium suggesting extracardiac hematoma vs. left atrium dissection. TC scan confirmed space compromise of the left atrium by a mass, without being able to rule out active bleeding. The patient was transferred to our center for emergent CABG surgery. Upon arrival, the patient had persistent chest pain, sinus tachycardia, and hypertension. Intraoperative TOE findings consisted of a mass compromising left atrium and minimal pericardium effusion. Comprehensive study identified a mobile intimal flap of the atrial wall that was creating a false chamber. Intraoperative surgery findings were compatible with a huge left atrial desiccant hematoma . Two orifices were performed on the epicardium of the inferior and lateral border of the left atrium, in order to drain the retained blood and lavage. No active bleeding was evidenced. TTE control evidenced disappearance of the left atrium mass a The patient had a satisfactory evolution and discharged without complications. Even though left atrial desiccant hematoma is a rare STEMI complication , in this patient, we concluded the etiology was iatrogenic due to the performance of PCI. Conclusion Left atrial dissection is an uncommon entity. It is generally associated with mitral valve replacement, but other predisposing factors should be considered in pathogenesis. Its diagnosis requires a high index of suspicion. Predisposing factors and catheterization, surgical or pathologic findings should be reviewed in order to identify the pathogenic mechanism . Dissection of the coronary sinus secondary to retrograde cardioplegia, endocarditis, cardiac rupture after myocardial infarction, blunt chest trauma and iatrogenic PCI are related to its development. Abstract 481 Figure. MASS COMPROMISIN LEFT ATRIUM </jats:sec

P1716 Aorto-left atrial fistula with left atrium dissection

Abstract We report a 71 year-old female with a history of rheumatic valvulopathy, who underwent St. Jude 23 and St. Jude 21 in mitral and aortic position replacement. The patient was admitted to the ER for pulmonary edema with haemoglobin level of 7.7 g/dL .No evidence of gastrointestinal bleeding. She was assessed to exclude intravascular hemolysis: bilirrubin 3.1mg/d,L direct bilirrubin 1.0 mg/dL, reticulocytes 207.000/mcL 6.8%, LDH 1.213, free plasmatic haemoglobin 9.6mg/dL, haptoglobin &amp;lt; 1 mg/dL, negative direct and indirect Coombs. Upon suspicion of hemolytic anemia in relation to prosthetic dysfunction, TEE was performed revealing stenotic mechanical aortic prosthesis with abundant pannus and normofunctional mitral prosthesis, no leakages were observed. A coronary CT scan showed severe calcification of the aortic root and mitral annulus without evidence of redundant tissue than hindered the opening of the aortic or mitral valves. Cardiac catheterization revealed normal coronary arteries, cardiac output preserved and mild passive predominance of PAP. Heart Team decided on aortic prosthesis valve replacement. On March 22, 2019 surgery was performed. There was a heavily calcified ascending aorta and aortic root with abundant pannus at the ventricular aspect of the aortic prosthesis. Former aortic prosthesis was resected and the root reconstructed with a pericardial patch. 18-mmATS mechanical aortic prosthesis was implanted. After 127minutes of cross-clamping time, the patient was admitted to the ICU. She presented a torpid course in the postoperative period after cardiac surgery and cardiogenic shock ensued. TEE was repeated, showing pseudoaneurysm of the mitral–aortic intervalvular fibrosa, left atrium dissection and severe paraprosthetic aortic leakage. Coronary CT scan revealed a large cavity, 7x4x3.5 cm, extending posteriorly and displacing cranially the right pulmonary artery and subsequently rejecting the cavity of left atrium; with final diagnosis of aorto-left atrial fistula with left atrium dissection. Emergent surgery was decided. During the procedure, mitral–aortic intervalvular fibrosa pseudoaneurysm was confirmed, perforation from the subaortic left ventricle into the left atrium was also appreciated at the junction of the aortic root pericardial patch with the dissected left atrium wall. Surgery was complicated with hemorrhagic shock and massive uncontrolled bleeding with severe coagulopathy and thrombocytopenia. The patient went into cardiac arrest and passed away in the operating room. Conclusion Aorto atrial fistulas are rare but important complications of many disease processes of the aorta and aortic valve. Classical clinical signs of continuous murmurs may not be present and echocardiography forms the cornerstone of diagnosis. AAF should be suspected in patients with poorly controlled heart failure and prior aortic surgery. Prompt surgical repair is usually helpful in relieving symptoms and decreasing mortality. Abstract P1716 Figure. Aortoatrial fistula </jats:sec

Screening of IRF6 Variants in Patients Subjected to Genetic Association Studies for Nonsyndromic Cleft Lip/Palate

Objective: To screen for interferon regulatory factor 6 (IRF6) pathogenic variants in patients clinically diagnosed with nonsyndromic cleft lip palate (NSCL/P) and establish the proportion of misdiagnosed Van der Woude syndrome (VWS) cases, which could have biased previous NSCL/P case–control association studies. Design: Retrospective case series. Setting: Tertiary care children’s hospital. Participants: One hundred seventy-two unrelated Mexican patients with NSCL/P, 128 of whom had previously been included in a NSCL/P case–control association study. Main Outcomes Measurements: Sanger sequencing of the 9 IRF6 exons were performed, all variants respect with sequence reference were reported and classified for their pathogenic significance according to the American College of Medical Genetics and Genomics guidelines. Results: Seven percent of cases were familial. No pathogenic variant was identified in IRF6. We identified 12 previously reported benign variants; their frequencies did not significantly differ from those reported for individuals of Mexican ancestry. Three of them were uncommon intronic variants not reported in ClinVar. The rs2235371 and rs2235375 variants, which were previously analyzed in a NSCL/P case–control association study (containing 132 patients, 128 of whom were analyzed herein) did not show discordant association results comparing to the 370 controls from the previous study. Conclusions: The misdiagnosis of IRF6-related VWS as NSCL/P appears to be infrequent in our sample, suggesting that mutational screening of IRF6 would have a low diagnostic yield in patients with NSCL/P. The absence of IRF6 pathogenic alleles could be related to the application of an exhaustive clinical evaluation that discarded the syndromic forms and/or the low proportion of familial cases included. </jats:sec

Gene Interactions Provide Evidence for Signaling Pathways Involved in Cleft Lip/Palate in Humans

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common craniofacial birth defect that has a complex etiology. Genome-wide association studies have recently identified new loci associated with NSCL/P, but these loci have not been analyzed in a Mexican Mestizo population. A complex etiology implies the presence of genetic interactions, but there is little available information regarding this in NSCL/P, and no signaling pathway has been clearly implicated in humans. Here, we analyzed the associations of 24 single nucleotide polymorphisms (SNPs) with NSCL/P in a Mexican Mestizo population (133 cases, 263 controls). The multifactorial dimensionality reduction method was used to examine gene–gene and gene–folic acid consumption interactions for the 24 SNPs analyzed in this study and for 2 additional SNPs that had previously been genotyped in the same study population. Six SNPs located in paired box 7, ventral anterior homeobox 1, sprouty RTK signaling antagonist 2, bone morphogenetic protein 4, and tropomyosin 1 genes were associated with higher risks of NSCL/P ( P = 0.0001 to 0.04); 2 SNPs, 1 each in netrin 1 and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, were associated with a lower risk of NSCL/P ( P = 0.013 to 0.03); and 2 SNPs, 1 each in ATP binding cassette subfamily A member 4 ( ABCA4) and noggin, showed associations with NSCL/P that approached the threshold of significance ( P = 0.056 to 0.07). In addition, 6 gene–gene interactions ( P = 0.0001 to 0.001) and an ABCA4–folic acid consumption interaction ( P &lt; 0.0001) were identified. On the basis of these results, combined with those of previous association studies in the literature and biological characterizations of murine models, we propose an interaction network in which interferon regulatory factor 6 plays a central role in the etiology of NSCL/P. </jats:p

Islands promote diversification of the silvereye species complex: a phylogenomic analysis of a great speciator

Geographic isolation plays a pivotal role in speciation by restricting gene flow between populations through distance or physical barriers. However, the speciation process is complex, influenced by the interplay between dispersal ability and geographic isolation, as seen in "great speciators" – bird species that simultaneously have broad island distributions but high levels of subspecific diversity. Comparing genomic population differentiation in species that occupy both continental and island settings can reveal the effects of different forms of geographic isolation and validate if the primary mechanism proposed to catalyse a great speciator pattern, that is dispersal reduction following island colonisation, has occurred. The highly diverse white-eye family Zosteropidae includes several great speciators, including the silvereye (Zosterops lateralis), with 16 subspecies (11 occurring on islands), distributed on the Australian continent and numerous southwest Pacific islands. We compared continental and island patterns of divergence using whole genome and morphological data. Australian mainland populations showed low genetic population structure, lack of isolation by distance patterns, and low morphological diagnosability, suggesting the species’ dispersal propensity in a continental setting is sufficient to overcome multiple forms of geographic barriers and large geographic distances. In contrast, except for island populations less than 200 years old, most island populations were highly genomically structured with clearer morphological diagnosability even if separated by relatively short geographic distances. The inferred reduction of dispersal propensity in island situations is consistent with the proposed model of great speciator formation on islands. Our phylogenomic analyses also allowed resolution of the silvereyes’ evolutionary position, showing their relatively early emergence (~1.5 Mya) within the rapidly radiating Zosteropidae, while population-level analyses demonstrated where morphological subspecies and genomic data align, and disagree. However, the silvereye example also shows how uncertainties about relationships remain when reconstructing evolutionary history in rapidly radiating groups, even when whole genome data is available. Altogether, our results show how within-species genomic and morphological patterns measured over broad spatial scales and with varying geographic contexts can help reveal when particular stages of speciation such as great speciators, are likely to emerge