Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical Outcomes in Hypoplastic Left Heart Syndrome.

OBJECTIVE: To determine the prevalence, spectrum, and prognostic significance of copy number variants of undetermined significance (cnVUS) seen on chromosomal microarray (CMA) in neonates with hypoplastic left heart syndrome (HLHS). STUDY DESIGN: Neonates with HLHS who presented to Texas Children's Hospital between June 2008 and December 2016 were identified. CMA results were abstracted and compared against copy number variations (CNVs) in ostensibly healthy individuals gathered from the literature. Findings were classified as normal, consistent with a known genetic disorder, or cnVUS. Survival was then compared using Kaplan-Meier analysis. Secondary outcomes included tracheostomy, feeding tube at discharge, cardiac arrest, and extracorporeal membrane oxygenation (ECMO). RESULTS: Our study cohort comprised 105 neonates with HLHS, including 70 (66.7%) with normal CMA results, 9 (8.6%) with findings consistent with a known genetic disorder, and 26 (24.7%) with a cnVUS. Six of the 26 (23.0%) neonates with a cnVUS had a variant that localized to a specific region of the genome seen in the healthy control population. One-year survival was 84.0% in patients with a cnVUS, 68.3% in those with normal CMA results, and 33.3% in those with a known genetic disorder (P = .003). There were no significant differences in secondary outcomes among the groups, although notably ECMO was used in 15.7% of patients with normal CMA and was not used in those with cnVUS and abnormal results (P = .038). CONCLUSIONS: Among children with HLHS, cnVUSs detected on CMA are common. The cnVUSs do not localize to specific regions of the genome, and are not associated with worse outcomes compared with normal CMA results.

First Report of the Armillaria Root-Disease Pathogen, Armillaria gallica, Associated with Several Woody Hosts in Three States of Mexico.

In September 2007, rhizomorphs with morphological characteristics of Armillaria were collected from woody hosts in forests of Mexico State, Veracruz, and Oaxaca, Mexico. Based on pairing tests, isolates were assigned to five somatically compatible genets or clones (MEX7R, MEX11R, MEX23R, MEX28R, and MEX30R). These genets were all identified as Armillaria gallica based on somatic pairing tests against known tester isolates and nucleotide sequences of the translation elongation factor 1α (tef-1α; GenBank Accession Nos. KF156772 to 76). Sequences of tef-1α for all genets showed a max identity of 97 to 99% to A. gallica (ST23, JF313125) (3,4). However, A. gallica comprises a genetically diverse complex that likely represents multiple cryptic species (3). In Mexico, this species has been previously reported in northeastern Morelos on Quercus sp., eastern Mexico State on Pinus hartwegii, and southwestern Mexico State on Prunus persica (1,2). This study identified associations with 10 new hosts within three states of Mexico, but only five hosts were diseased. Genet MEX7R comprised seven isolates collected in the University of Chapingo forest near Texcoco, Mexico State (19°18'10.764″ N, 98°42'14.147″ W, elevation 3441 m). Four MEX7R isolates were collected from diseased Alnus sp. including the root ball of a 130 cm dbh, root-disease killed tree, one isolate from a symptomless Senecio sp. s.l. (Roldana sp.) shrub and two isolates from symptomless Abies religiosa. Genet MEX11R comprised four isolates from a cloud forest near Xalapa, Veracruz (19°31'14.628″ N, 96°59'22.812″ W, elevation 1496 m). MEX11R isolates were collected from the roots of a root-disease killed Carpinus caroliniana, and from trees with no obvious symptoms (Miconia mexicana, Quercus xalapensis, and Liquidambar styraciflua). Two isolates of genet MEX23R were collected from the Jardin Botanico Francisco Javier Clavijero, Instituto de Ecologia, A.C., Xalapa, Veracruz (19°30'49.067″ N, 96°56'32.999″ W, elevation 1344 m). These isolates were from root-diseased Eriobotrya japonica (non-native fruit tree) that showed obvious symptoms (flaccid, chlorotic, and senescing leaves) and from an adjacent, infected Platanus mexicana that did not show readily observable symptoms. Two collections near Oaxaca, Oaxaca, included a single isolate MEX28R from the root ball of a recently root disease-killed Arbutus xalapensis within a small root disease center at Peña Prieta, in Parque La Cumbre, near Ixtepeji (17°09'42.084″ N, 96°38'15.936″ W, elevation 2853 m) and a single isolate MEX30R from the base of an asymptomatic Alnus acuminata near the El Carrizal fish hatchery 10 km northeast of San Miguel del Valle (17°06'45.036″ N, 96°24'03.743″ W, elevation 2594 m). Armillaria gallica has a circumpolar distribution with an extremely wide host range, and its ecological behavior varies greatly. Continued surveys are needed to better understand the distribution and ecological impacts of this pathogen in relation to Armillaria root disease in Mexico and the potential influences of climate change. Although A. gallica displays diverse ecological behavior, trees infected with A. gallica are less likely to survive the stresses of human activity and a changing climate (4). References: (1) D. Alvarado-Rosales and R. A. Blanchette. Phytopathology 84:1106, 1994. (2) R. D. Elias-Roman et al. For. Pathol. 43:390, 2013. (3) M.-S. Kim et al. Phytopathology 102:S4.63, 2012. (4) B. Marcais and N. Breda. J. Ecol. 94:1214, 2006.

First Report of Armillaria Root Disease Caused by Armillaria tabescens on Araucaria araucana in Veracruz, Mexico.

In September 2007, bark samples were collected from the root collar of a single Araucaria araucana tree that had recently died and was suspected of being killed by Armillaria root disease. Disease symptoms and signs included a thinning crown and fruiting bodies at the tree base over a several-year period before tree death. The tree was located in an isolated street-tree planting within a business district on Maestros Veracruzanos Street, Xalapa, Veracruz (19°31'52''N, 96°54'25''W, elevation 1,392 m). One fungal isolate (MEX21WF) was obtained, which possessed two sequence repeat types from the intergenic spacer-1 (IGS-1) region (GenBank Accession Nos. GQ335541 and GQ335542). On the basis of these IGS-1 sequences, this isolate from Mexico possessed 99% nucleotide sequence identities with North American Armillaria tabescens isolates (GenBank Accession Nos. AY695410 ≈ GQ335541 and AY773966 ≈ GQ335542). Somatic pairing tests of the isolate with other North American Armillaria species also identified it as A. tabescens (2). In addition, fruiting bodies were produced on the stump base in 2009 that matched morphological features of A. tabescens, e.g., exannulate, cespitose growth in clusters, brown-gray stipe to blackish toward the base, longitudinally fibrillose, basidiospores (6-) 7 to 9 × 4 to 5 (-5.5) µm, and other general morphology. On the basis of these three lines of taxonomic evidence, it was concluded that the isolate was A. tabescens. To our knowledge, this is the first confirmed report of A. tabescens causing Armillaria root disease in Mexico. Furthermore, this note represents the first report of A. tabescens on Araucaria araucana, which is native to Chile and Argentina. The other previous reports of A. tabescens in Mexico are based on herbarium specimens collected in 1965 (BPI 753040) from Valle de Bravo (approximately 350 km west of Xalapa) in the state of México and 1973 (BPI 753041) from near Monterrey (approximately 760 km north-northwest of Xalapa) in the state of Nuevo León (1). However, no host information or confirmation of taxonomic identification was reported for these herbarium specimens. Although this note confirms the presence of A. tabescens in Mexico, more surveys and monitoring are needed to determine the full distribution of this pathogen in Mexico. Because the climate and tree communities of eastern Mexico are similar to those of the southeastern United States, where A. tabescens has been reported as a common pathogen of oaks and fruit trees (3,4), it seems reasonable that A. tabescens may represent an existing or potential threat in eastern Mexico. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory. Online publication. ARS, USDA, 2010. (2) K. I. Mallett and Y. Hiratsuka. Can. J. Bot. 64:2588, 1986. (3) F. Miranda and A. J. Sharp. Ecology 31:313, 1950. (4) G. Schnabel et al. Mycol. Res. 109:1208, 2005.

Use of coca leaf in southern Peru: adaptation or addiction.

Use of coca leaves among the Quechua Indians of the Peruvian altiplano is considered from the biological and social perspectives. Biologically, coca use seems to reduce the loss of body heat in the cold and to enhance working ability to a small degree. It may also have nutritional value. Socially, coca is well integrated into the economic and social systems, providing functions in both spheres. The equation of coca use with cocaine addiction is also considered and a simple equivalence is rejected.