Biogeographic history of a large clade of ectomycorrhizal fungi, the Russulaceae, in the Neotropics and adjacent regions.

The biogeography of neotropical fungi remains poorly understood. Here, we reconstruct the origins and diversification of neotropical lineages in one of the largest clades of ectomycorrhizal fungi in the globally widespread family Russulaceae. We inferred a supertree of 3285 operational taxonomic units, representing worldwide internal transcribed spacer sequences. We reconstructed biogeographic history and diversification and identified lineages in the Neotropics and adjacent Patagonia. The ectomycorrhizal Russulaceae have a tropical African origin. The oldest lineages in tropical South America, most with African sister groups, date to the mid-Eocene, possibly coinciding with a boreotropical migration corridor. There were several transatlantic dispersal events from Africa more recently. Andean and Central American lineages mostly have north-temperate origins and are associated with North Andean uplift and the general north-south biotic interchange across the Panama isthmus, respectively. Patagonian lineages have Australasian affinities. Diversification rates in tropical South America and other tropical areas are lower than in temperate areas. Neotropical Russulaceae have multiple biogeographic origins since the mid-Eocene involving dispersal and co-migration. Discontinuous distributions of host plants may explain low diversification rates of tropical lowland ectomycorrhizal fungi. Deeply diverging neotropical fungal lineages need to be better documented.

Idiopathic recurrent serositis-Off the beaten track.

A 63-year-old female presented with chest pain and fever, and was found to have recurrent pleuropericardial effusions. Extensive investigations including infection screen and serologies, autoimmune screen and pleural and pericardial biopsy revealed no secondary aetiologies. She was diagnosed with idiopathic recurrent serositis (IRS). Our patient developed rash to naproxen, so she was started on colchicine monotherapy and responded well clinically. A review of the literature demonstrated that pleuropericardial effusions are rare occurrences, with patients occasionally being perceived as a medical enigma. This case study recommends an approach to guide physicians in their diagnosis and management of patients with pleuropericardial syndrome. Our case had an inflammatory phenotype, either autoimmune or seronegative serositis of unclear aetiology, which was recurrent and required pharmacological treatment. While the treatment for IRS lies in combined therapy with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and colchicine, monotherapy with colchicine was effective in the treatment and preventing recurrence in our unique case.

Cascading effects of moth outbreaks on subarctic soil food webs.

The increasing severity and frequency of natural disturbances requires a better understanding of their effects on all compartments of biodiversity. In Northern Fennoscandia, recent large-scale moth outbreaks have led to an abrupt change in plant communities from birch forests dominated by dwarf shrubs to grass-dominated systems. However, the indirect effects on the belowground compartment remained unclear. Here, we combined eDNA surveys of multiple trophic groups with network analyses to demonstrate that moth defoliation has far-reaching consequences on soil food webs. Following this disturbance, diversity and relative abundance of certain trophic groups declined (e.g., ectomycorrhizal fungi), while many others expanded (e.g., bacterivores and omnivores) making soil food webs more diverse and structurally different. Overall, the direct and indirect consequences of moth outbreaks increased belowground diversity at different trophic levels. Our results highlight that a holistic view of ecosystems improves our understanding of cascading effects of major disturbances on soil food webs.

Identification and dereplication of endophytic Colletotrichum strains by MALDI TOF mass spectrometry and molecular networking.

The chemical diversity of biologically active fungal strains from 42 Colletotrichum, isolated from leaves of the tropical palm species Astrocaryum sciophilum collected in pristine forests of French Guiana, was investigated. The collection was first classified based on protein fingerprints acquired by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) correlated with cytotoxicity. Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS) data from ethyl acetate extracts were acquired and processed to generate a massive molecular network (MN) using the MetGem software. From five Colletotrichum strains producing cytotoxic specialized metabolites, we predicted the occurrence of peptide and cytochalasin analogues in four of them by MN, including a similar ion clusters in the MN algorithm provided by MetGem software. Chemoinformatics predictions were fully confirmed after isolation of three pentacyclopeptides (cyclo(Phe-Leu-Leu-Leu-Val), cyclo(Phe-Leu-Leu-Leu-Leu) and cyclo(Phe-Leu-Leu-Leu-Ile)) and two cytochalasins (cytochalasin C and cytochalasin D) exhibiting cytotoxicity at the micromolar concentration. Finally, the chemical study of the last active cytotoxic strain BSNB-0583 led to the isolation of four colletamides bearing an identical decadienamide chain.

Fungi of French Guiana gathered in a taxonomic, environmental and molecular dataset.

In Amazonia, the knowledge about Fungi remains patchy and biased towards accessible sites. This is particularly the case in French Guiana where the existing collections have been confined to few coastal localities. Here, we aimed at filling the gaps of knowledge in undersampled areas of this region, particularly focusing on the Basidiomycota. From 2011, we comprehensively collected fruiting-bodies with a stratified and reproducible sampling scheme in 126 plots. Sites of sampling reflected the main forest habitats of French Guiana in terms of soil fertility and topography. The dataset of 5219 specimens gathers 245 genera belonging to 75 families, 642 specimens are barcoded. The dataset is not a checklist as only 27% of the specimens are identified at the species level but 96% are identified at the genus level. We found an extraordinary diversity distributed across forest habitats. The dataset is an unprecedented and original collection of Basidiomycota for the region, making specimens available for taxonomists and ecologists. The database is publicly available in the GBIF repository ( https://doi.org/10.15468/ymvlrp ).

Coordinated community structure among trees, fungi and invertebrate groups in Amazonian rainforests.

Little is known regarding how trophic interactions shape community assembly in tropical forests. Here we assess multi-taxonomic community assembly rules using a rare standardized coordinated inventory comprising exhaustive surveys of five highly-diverse taxonomic groups exerting key ecological functions: trees, fungi, earthworms, ants and spiders. We sampled 36 1.9-ha plots from four remote locations in French Guiana including precise soil measurements, and we tested whether species turnover was coordinated among groups across geographic and edaphic gradients. All species group pairs exhibited significant compositional associations that were independent from soil conditions. For some of the pairs, associations were also partly explained by soil properties, especially soil phosphorus availability. Our study provides evidence for coordinated turnover among taxonomic groups beyond simple relationships with environmental factors, thereby refining our understanding regarding the nature of interactions occurring among these ecologically important groups.

Facilitation of Balsam Fir by Trembling Aspen in the Boreal Forest: Do Ectomycorrhizal Communities Matter?

Succession is generally well described above-ground in the boreal forest, and several studies have demonstrated the role of interspecific facilitation in tree species establishment. However, the role of mycorrhizal communities for tree establishment and interspecific facilitation, has been little explored. At the ecotone between the mixed boreal forest, dominated by balsam fir and hardwood species, and the boreal forest, dominated by black spruce, several stands of trembling aspen can be found, surrounded by black spruce forest. Regeneration of balsam fir seems to have increased in the recent decades within the boreal forest, and it seems better adapted to grow in trembling aspen stands than in black spruce stands, even when located in similar abiotic conditions. As black spruce stands are also covered by ericaceous shrubs, we investigated if differences in soil fungal communities and ericaceous shrubs abundance could explain the differences observed in balsam fir growth and nutrition. We conducted a study centered on individual saplings to link growth and foliar nutrient concentrations to local vegetation cover, mycorrhization rate, and mycorrhizal communities associated with balsam fir roots. We found that foliar nutrient concentrations and ramification indices (colonization by mycorrhiza per length of root) were greater in trembling aspen stands and were positively correlated to apical and lateral growth of balsam fir saplings. In black spruce stands, the presence of ericaceous shrubs near balsam fir saplings affected ectomycorrhizal communities associated with tree roots which in turn negatively correlated with N foliar concentrations. Our results reveal that fungal communities observed under aspen are drivers of balsam fir early growth and nutrition in boreal forest stands and may facilitate ecotone migration in a context of climate change.

Hidden fungal diversity from the Neotropics: Geastrum hirsutum, G. schweinitzii (Basidiomycota, Geastrales) and their allies.

Taxonomy of Geastrum species in the neotropics has been subject to divergent opinions among specialists. In our study, type collections were reassessed and compared with recent collections in order to delimit species in Geastrum, sect. Myceliostroma, subsect. Epigaea. A thorough review of morphologic features combined with barcode and phylogenetic analyses (ITS and LSU nrDNA) revealed six new species (G. neoamericanum, G. rubellum, G. brunneocapillatum, G. baculicrystallum, G. rubropusillum and G. courtecuissei). In additon, the presence of hairs on the exoperidium, a commonly used feature to diagnose Geastrum species, proved to be ineffective because it is a derived character within subsect. Epigaea.

Fungal communities associated with Evernia prunastri, Ramalina fastigiata and Pleurosticta acetabulum: Three epiphytic lichens potentially active against Candida biofilms.

Fungal communities associated to three epiphytic lichens active against Candida, were investigated using culture-based methods We hypothetized that associated fungi would contribute to lichens activities. The ability of specific fungi to grow inside or outside lichens was investigated. To detect biogenesis pathways involved in the production of secondary metabolites, genes coding for nonribosomal peptide synthetase (NRPS) and polyketide synthase I (PKS I) were screened by PCR from fungal DNA extracts. Both endo and epilichenic communities were isolated from two fructicose (Evernia prunastri and Ramalina fastigiata) and one foliose (Pleurosticta acetabulum) lichens. A total of 86 endolichenic and 114 epilichenic isolates were obtained, corresponding to 18 and 24 phylogenetic groups respectively suggesting a wide diversity of fungi. The communities and the species richness were distinct between the three lichens which hosted potentially new fungal species. Additionally, the endo- and epilichenic communities differed in their composition: Sordariomycetes were particularly abundant among endolichenic fungi and Dothideomycetes among epilichenic fungi. Only a few fungi colonized both habitats, such as S. fimicola, Cladosporium sp1 and Botrytis cinerea. Interestingly, Nemania serpens (with several genotypes) was the most abundant endolichenic fungus (53% of isolates) and was shared by the three lichens. Finally, 12 out of 36 phylogenetic groups revealed the presence of genes coding for nonribosomal peptide synthetase (NRPs) and polyketide synthase I (PKS I). This study shows that common lichens are reservoirs of diverse fungal communities, which could potentially contribute to global activity of the lichen and, therefore, deserve to be isolated for further chemical studies.

Drivers of vegetative dormancy across herbaceous perennial plant species.

Vegetative dormancy, that is the temporary absence of aboveground growth for ≥ 1 year, is paradoxical, because plants cannot photosynthesise or flower during dormant periods. We test ecological and evolutionary hypotheses for its widespread persistence. We show that dormancy has evolved numerous times. Most species displaying dormancy exhibit life-history costs of sprouting, and of dormancy. Short-lived and mycoheterotrophic species have higher proportions of dormant plants than long-lived species and species with other nutritional modes. Foliage loss is associated with higher future dormancy levels, suggesting that carbon limitation promotes dormancy. Maximum dormancy duration is shorter under higher precipitation and at higher latitudes, the latter suggesting an important role for competition or herbivory. Study length affects estimates of some demographic parameters. Our results identify life historical and environmental drivers of dormancy. We also highlight the evolutionary importance of the little understood costs of sprouting and growth, latitudinal stress gradients and mixed nutritional modes.

A pantropically introduced tree is followed by specific ectomycorrhizal symbionts due to pseudo-vertical transmission.

Global trade increases plant introductions, but joint introduction of associated microbes is overlooked. We analyzed the ectomycorrhizal fungi of a Caribbean beach tree, seagrape (Coccoloba uvifera, Polygonacaeae), introduced pantropically to stabilize coastal soils and produce edible fruits. Seagrape displays a limited symbiont diversity in the Caribbean. In five regions of introduction (Brazil, Japan, Malaysia, Réunion and Senegal), molecular barcoding showed that seagrape mostly or exclusively associates with Scleroderma species (Basidiomycota) that were hitherto only known from Caribbean seagrape stands. An unknown Scleroderma species dominates in Brazil, Japan and Malaysia, while Scleroderma bermudense exclusively occurs in Réunion and Senegal. Population genetics analysis of S. bermudense did not detect any demographic bottleneck associated with a possible founder effect, but fungal populations from regions where seagrape is introduced are little differentiated from the Caribbean ones, separated by thousands of kilometers, consistently with relatively recent introduction. Moreover, dry seagrape fruits carry Scleroderma spores, probably because, when drying on beach sand, they aggregate spores from the spore bank accumulated by semi-hypogeous Scleroderma sporocarps. Aggregated spores inoculate seedlings, and their abundance may limit the founder effect after seagrape introduction. This rare pseudo-vertical transmission of mycorrhizal fungi likely contributed to efficient and repeated seagrape/Scleroderma co-introductions.

Patterns of diversity, endemism and specialization in the root symbiont communities of alder species on the island of Corsica.

We investigated whether the diversity, endemicity and specificity of alder symbionts could be changed by isolation in a Mediterranean glacial refugium. We studied both ectomycorrhizal (EM) fungi and nitrogen-fixing actinobacteria associated with alders, and compared their communities in Corsica and on the European continent. Nodules and root tips were sampled on the three alder species present in Corsica and continental France and Italy. Phylogenies based on internal transcribed spacer (ITS) and a multilocus sequence analysis approach were used to characterize fungal and Frankia species, respectively. Patterns of diversity, endemism and specialization were compared between hosts and regions for each symbiont community. In Corsica, communities were not generally richer than on the mainland. The species richness per site depended mainly on host identity: Alnus glutinosa and Alnus cordata hosted richer Frankia and EM communities, respectively. Half of the Frankia species were endemic to Corsica against only 4% of EM species. Corsica is not a hotspot of diversity for all alder symbionts but sustains an increased frequency of poor-dispersers such as hypogeous fungi. Generalist EM fungi and host-dependent profusely sporulating (Sp+) Frankia were abundantly associated with Corsican A. cordata, a pattern related to a more thermophilic and xerophylic climate and to the co-occurrence with other host trees.

Alder and the Golden Fleece: high diversity of Frankia and ectomycorrhizal fungi revealed from Alnus glutinosa subsp. barbata roots close to a Tertiary and glacial refugium.

BACKGROUND: Recent climatic history has strongly impacted plant populations, but little is known about its effect on microbes. Alders, which host few and specific symbionts, have high genetic diversity in glacial refugia. Here, we tested the prediction that communities of root symbionts survived in refugia with their host populations. We expected to detect endemic symbionts and a higher species richness in refugia as compared to recolonized areas. METHODS: We sampled ectomycorrhizal (EM) root tips and the nitrogen-fixing actinomycete Frankia communities in eight sites colonized by Alnus glutinosa subsp. barbata close to the Caucasus in Georgia. Three sites were located in the Colchis, one major Eurasian climatic refugia for Arcto-Tertiary flora and alders, and five sites were located in the recolonized zone. Endemic symbionts and plant ITS variants were detected by comparing sequences to published data from Europe and another Tertiary refugium, the Hyrcanian forest. Species richness and community structure were compared between sites from refugia and recolonized areas for each symbionts. RESULTS: For both symbionts, most MOTUs present in Georgia had been found previously elsewhere in Europe. Three endemic Frankia strains were detected in the Colchis vs two in the recolonized zone, and the five endemic EM fungi were detected only in the recolonized zone. Frankia species richness was higher in the Colchis while the contrary was observed for EM fungi. Moreover, the genetic diversity of one alder specialist Alnicola xanthophylla was particularly high in the recolonized zone. The EM communities occurring in the Colchis and the Hyrcanian forests shared closely related endemic species. DISCUSSION: The Colchis did not have the highest alpha diversity and more endemic species, suggesting that our hypothesis based on alder biogeography may not apply to alder's symbionts. Our study in the Caucasus brings new clues to understand symbioses biogeography and their survival in Tertiary and ice-age refugia, and reveals that isolated host populations could be of interest for symbiont diversity conservation.

Demographic shifts related to mycoheterotrophy and their fitness impacts in two Cephalanthera species.

Evolutionary losses of photosynthesis in terrestrial plants all originate in photosynthetic ancestors. The adaptive context under which this transition happens has remained elusive because of the rarity of plants in which both photosynthetic and non-photosynthetic forms exist as a polymorphism. Here, we report on demographic patterns in photosynthetic ("green") and nonphotosynthetic ("albino") individuals within populations of two such species, Cephalanthera damasonium and C. longifolia, which also acquire nutrition from their mycorrhizal hosts (partial mycoheterotrophy). We hypothesized that demographic shifts in albinos relative to greens would include compensatory patterns with respect to fitness, such that maladaptive changes to survival or reproduction would be adaptively countered by changes to other parameters, such as growth probabilities. We tracked individuals in two populations of C. damasonium for 3 yr, and in one population of C. longifolia for 14 yr. We then analyzed vital rates for both phenotypes using general linear mixed models (GLMMs) and multi-state capture mark-recapture models (CMR), and used these models to develop size-classified, function-based population projection matrices. We estimated fitness as the deterministic population growth rate (λ) for each phenotype, and explored the impact of shifts in demographic patterns to albinism via life table response experiments (LTREs). Mortality differed between greens and albinos, but not similarly across species. Albinos generally sprouted less than greens, and flowered more when small but less at other times. Albinos typically had a higher probability of fruiting, although their lower flower numbers yielded lower numbers of fruits overall. Fitness did not differ significantly among phenotypes. Thus, we did not find significant evidence that albinism is adaptive or maladaptive; however, if in fact it is the latter, then we did find evidence of incomplete compensation for declines in survival and reproduction from growth transitions, particularly to small flowering size classes in C. damasonium, and to large vegetative size classes in C. longifolia. These patterns indicate some support for the idea that albinism may lead to the speciation of mycoheterotrophic plants.

Prediction and impact of failure of transradial approach for primary percutaneous coronary intervention.

OBJECTIVES: To determine predictors of failure of transradial approach (TRA) in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and develop a novel score specific for this population. METHODS: Consecutive patients with STEMI undergoing primary PCI in a tertiary care high-volume radial centre were included. TRA-PCI failure was categorised as primary (primary transfemoral approach (TFA)) or crossover (from TRA to TFA). Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed. Clinical outcomes up to 1 year were assessed. RESULTS: From January 2006 to January 2011, 2020 patients were studied. Primary TRA-PCI failure occurred in 111 (5%) patients and crossover to TFA in 44 (2.2%) patients. Independent predictors of TRA-PCI failure were: weight ≤65 kg (OR: 3.0; 95% CI 1.9 to 4.8, p<0.0001), physician with ≤5% TFA conversion (OR: 0.45; 95% CI 0.2 to 0.9, p=0.033), and physician with ≥10% conversion to TFA (OR: 2.2; 95% CI 1.2 to 3.7, p=0.005), intra-aortic balloon pump (OR: 2.0; 95% CI 0.9 to 4.3, p=0.066), cardiogenic shock (OR: 2.8; 95% CI 1.4 to 5.6, p=0.0035), endotracheal intubation (OR: 107; 95% CI 42 to 339, p<0.0001), creatinine >133 µmol/L (OR: 3.6; 95% CI 1.9 to 6.8, p<0.0001), age ≥75 (OR: 1.7; 95% CI 1.0 to 2.9, p=0.031), prior PCI (OR: 2.6; 95% CI 1.5 to 4.5, p=0.0009), hypertension (OR: 1.8; 95% CI 1.2 to 2.9, p=0.009). An integer risk score ranging from -1 to 12 was developed, and predicted TRA-PCI failure from 0% to 100% (c-statistic of 0.868; 95% CI 0.866 to 0.869). Mortality at 1 year remained significantly higher after TRA-PCI failure (adjusted OR 2.2; 95% CI 1.2 to 3.9, p=0.011). CONCLUSIONS: In a high-volume radial centre, the incidence of TRA-PCI failure is low and can be accurately predicted using a 9-variables risk score. Since outcomes after TRA-PCI failure remained inferior, further effort to maximise the use of radial approach for primary PCI should be investigated.

Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity.

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the prevention of cardiovascular events following percutaneous coronary intervention (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent these events, proton pump inhibitors (PPI) are routinely prescribed. It has been reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 enzyme activity (phenotype) and its correlation with platelet reactivity following PPI therapy has not yet been fully described. In this study we attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the administration of PPI in coronary artery disease (CAD) patients treated with DAPT after PCI. Thirty (30) days after successful PCI with stent placement, 59 patients enrolled in the Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov Identifier: NCT00930670) were recruited to participate in this sub study. Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet function was evaluated by vasodilator-stimulated phosphoprotein (VASP) phosphorylation and light transmittance aggregometry before and 30 d after treatment with antacid therapy. Patients randomized to esomeprazole and omeprazole had greater high on-treatment platelet reactivity and lowering of CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized to ranitidine and pantoprazole did not show any changes in platelet activity or CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, changes in CYP2C19 enzyme activity (phenoconversion) correlated well with changes in platelet reactivity. Co-administration of omeprazole or esomeprazole in patients treated with clopidogrel results in lower CYP2C19 enzyme activity and increased platelet reactivity as measured by VASP phosphorylation test while patients given pantoprazole or ranitidine did not show any significant changes in CYP2C19 enzyme activity and platelet reactivity.

Interaction between vitamin B6 and source of selenium on the response of the selenium-dependent glutathione peroxidase system to oxidative stress induced by oestrus in pubertal pig.

This study aimed to assess the interaction between vitamin B6 and selenium (Se) for the flow of Se towards the Se-dependent glutathione peroxidase (GPX) system in response to oxidative stress naturally induced by oestrus in a pubertal pig model. At first oestrus, forty-five gilts were randomly assigned to the experimental diets (n=9/group): basal diet (CONT); CONT+0.3mg/kg of Na-selenite (MSeB60); MSeB60+10mg/kg of HCl-B6 (MSeB610); CONT+0.3mg/kg of Se-enriched yeast (OSeB60); and OSeB60+10mg/kg of HCl-B6 (OSeB610). Blood samples were collected at each oestrus (long-term profiles), and daily from day -4 to +3 (slaughter) of the fourth oestrus (peri-oestrus profiles) after which liver, kidneys, and ovaries were collected. For long-term profiles, CONT had lower blood Se than Se-supplemented gilts (p<0.01) and OSe was higher than MSe (p<0.01). Lower erythrocyte pyridoxal-5-phosphate was found in B60 than B610 (p<0.01). No treatment effect was observed on GPX activity. For peri-oestrus profiles, treatment effects were similar to long-term profiles. Treatment effects on liver Se were similar to those for long-term blood Se profiles and OSe had higher renal Se concentrations than MSe gilts (p<0.01). Gene expressions of GPX1, GPX3, GPX4, and selenocysteine lyase in liver and kidney were greatest in OSeB610 gilts (p<0.05). These results suggest that dietary B6 modulate the metabolic pathway of OSe towards the GPX system during the peri-oestrus period in pubertal pigs.

Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.

IMPORTANCE: Retinal detachment with avascularity of the peripheral retina, typically associated with familial exudative vitreoretinopathy (FEVR), can result from mutations in KIF11, a gene recently identified to cause microcephaly, lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal dysplasia, microcephaly, and mental retardation (CDMMR). Ophthalmologists should be aware of the range of presentations for mutations in KIF11 because the phenotypic distinction between FEVR and MLCRD/CDMMR portends management implications in patients with these conditions. OBJECTIVE: To identify gene mutations in patients who present with a FEVR phenotype and explore the spectrum of ocular and systemic abnormalities caused by KIF11 mutations in a cohort of patients with FEVR or microcephaly in conjunction with chorioretinopathy or FEVR. DESIGN, SETTING, AND PARTICIPANTS: Clinical data and DNA were collected from each participant between 1998 and 2013 from the clinical practices of ophthalmologists and clinical geneticists internationally. Twenty-eight FEVR probands with diagnoses made by the referring physician and without a known FEVR gene mutation, and 3 with microcephaly and chorioretinopathy, were included. At least 1 patient in each pedigree manifested 1 or more of the following: macular dragging, partial retinal detachment, falciform folds, or total retinal detachment. EXPOSURES: Whole-exome sequencing was conducted on affected members in multiplex pedigrees, and Sanger sequencing of the 22 exons of the KIF11 gene was performed on singletons. Clinical data and history were collected and reviewed. MAIN OUTCOMES AND MEASURES: Identification of mutations in KIF11. RESULTS: Four novel heterozygous KIF11 mutations and 1 previously published mutation were identified in probands with FEVR: p.A218Gfs*15, p.E470X, p.R221G, c.790-1G>T, and the previously described heterozygous p.R47X. Documentation of peripheral avascular areas on intravenous fluorescein angiography was possible in 2 probands with fibrovascular proliferation demonstrating phenotypic overlap with FEVR. CONCLUSIONS AND RELEVANCE: Mutations in KIF11 cause a broader spectrum of ocular disease than previously reported, including retinal detachment. The KIF11 gene likely plays a role in retinal vascular development and mutations in this gene can lead to clinical overlap with FEVR. Cases of FEVR should be carefully inspected for the presence of microcephaly as a marker for KIF11-related disease to enhance the accuracy of the prognosis and genetic counseling.