RESUMEN
In the face of climate-induced challenges, understanding the intricate molecular mechanisms underlying drought tolerance in plants has become imperative [...].
Asunto(s)
Sequías , Seguridad Alimentaria , Estrés Fisiológico , Plantas/genética , Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Fenómenos Fisiológicos de las PlantasRESUMEN
Increasing exposure to unfavorable temperatures and water deficit imposes major constraints on most crops worldwide. Despite several studies regarding coffee responses to abiotic stresses, transcriptome modulation due to simultaneous stresses remains poorly understood. This study unravels transcriptomic responses under the combined action of drought and temperature in leaves from the two most traded species: Coffea canephora cv. Conilon Clone 153 (CL153) and C. arabica cv. Icatu. Substantial transcriptomic changes were found, especially in response to the combination of stresses that cannot be explained by an additive effect. A large number of genes were involved in stress responses, with photosynthesis and other physiologically related genes usually being negatively affected. In both genotypes, genes encoding for protective proteins, such as dehydrins and heat shock proteins, were positively regulated. Transcription factors (TFs), including MADS-box genes, were down-regulated, although responses were genotype-dependent. In contrast to Icatu, only a few drought- and heat-responsive DEGs were recorded in CL153, which also reacted more significantly in terms of the number of DEGs and enriched GO terms, suggesting a high ability to cope with stresses. This research provides novel insights into the molecular mechanisms underlying leaf Coffea responses to drought and heat, revealing their influence on gene expression.
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Coffea , Sequías , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Calor , Transcriptoma , Coffea/genética , Coffea/metabolismo , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , GenotipoRESUMEN
OBJECTIVE: To determine the association of patient-level characteristics on the use of a patient engagement technology during the perioperative period. SUMMARY OF BACKGROUND DATA: As implementation of patient engagement technologies continues to grow, it remains unclear who uses, and not uses, these technologies. Existing literature suggests significant disparities in usage of other technologies by patient age, race, sex, and geographic location, however, have yet to characterize patient usage of patient engagement technologies. METHODS: This is a retrospective cohort study of patients undergoing elective surgery by a colorectal surgeon between January 2018 and March 2020 who enrolled in a patient engagement technology at a single institution. Patients enrolled received educational content, healthcare reminders, patient reported outcome (PRO) surveys, and health checks preoperatively, in-hospital, and for 30-days postdischarge. The primary outcome was patient activation of the patient engagement technology. Secondary outcomes were completion of at least 1 PRO survey, 1 in-hospital health check, and 1 postdischarge health check. RESULTS: Of 549 patients who enrolled in the patient engagement technology, 473 (86.2%) activated. On multivariable stepwise regression, female patients [odds ratio (OR) 2.4, confidence interval (CI) 1.4-4.0, P = 0.001] and privately insured patients (OR 2.0, CI 1.1-3.8, P = 0.03) were more likely to activate. Black patients were less likely to activate (OR 0.5, CI 0.3-0.9, P = 0.02). Once activated, privately insured patients were more likely to complete PRO surveys (OR 2.3, CI 1.2-4.3, P = 0.01), in-hospital health checks (OR 2.4, CI 1.4-4.1, P = 0.002), and postdischarge health checks (OR 1.9, CI 1.1 -3.3, P < 0.001) than uninsured patients. Black patients were less likely to complete PRO surveys (OR 0.4, CI 0.3-0.7, P = 0.001) and in-hospital health checks (OR 0.6, CI 0.4-0.9, P = 0.03) than White patients. CONCLUSIONS: Use of a patient engagement technology in the perioperative period differs significantly by sex, race/ethnicity, and insurance status. These technologies may not be used equally by all patients, which should be considered during implementation of interventions to improve surgical outcomes.
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Cuidados Posteriores , Participación del Paciente , Humanos , Femenino , Estados Unidos , Estudios Retrospectivos , Alta del Paciente , Etnicidad , Disparidades en Atención de SaludRESUMEN
BACKGROUND: Sea-lavenders (Limonium Mill., Plumbaginaceae) are a cosmopolitan group of diploid and polyploid plants often adapted to extreme saline environments, with a mostly Tethyan distribution, occurring in the Mediterranean, Irano-Turanian, Euro-Siberian and in the New World. The halophylic Limonium vulgare polyploid complex in particular, presents a large distribution throughout extreme salt-marsh habitats and shows little morphological but high taximetric variation, frequently blurring species delimitation. In this work we pursue three main goals: assert whether SNP data from polyploid individuals has the resolution to distinguish the seven sampled species, to better understand how genetically structured Limonium vulgare is, and attempt to identify specific molecular mechanisms for the differentiation between L. maritimum and L. vulgare. For this purpose, 95 individuals were genotyped using Genotyping by Sequencing (GBS), which were assembled as two independent datasets using IPYRAD. All analyses performed downstream of assembly were fully automated. Phylogenetic inference, PCA, and admixture plots were used to infer answers to the study's main goals. RESULTS: Close to 10,000 SNPs were obtained for each dataset. Phylogenetic analyses reveal that polyploid data can be used to infer species relationships. Population structure analyses suggest a genetically structured L. vulgare. A set of 34 SNPs were found to be fully segregated between L. vulgare and L. maritimum, two of which are potentially linked to proteins that might be involved in the speciation process. CONCLUSION: Despite polyploid data analyses shortcomings, GBS generated SNPs have the resolution to discern all seven included species. Limonium vulgare revealed pronounced genetic structure along a geographical north-south cline. L. maritimum always appears as a distinct genetic entity. Segregated SNPs between L. vulgare and L. maritimum indicate salinity response and morphological trait control genes as potentially interesting to follow up for studying these species' divergence process.
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Lavandula , Plumbaginaceae , Filogenia , Plumbaginaceae/genética , Polimorfismo de Nucleótido Simple/genética , Variación Genética , Poliploidía , GenómicaRESUMEN
We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ2 test), but mostly outside the functional domains (p = 0.004; χ2 test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.
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Blefarofimosis , Discapacidad Intelectual , Discapacidad Intelectual Ligada al Cromosoma X , Masculino , Humanos , Complejo Mediador/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Blefarofimosis/genética , Mutación Missense/genética , Fenotipo , SíndromeRESUMEN
Ongoing climate change poses a great risk to the natural environment and the sustainability of agriculture [...].
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Cambio Climático , Ambiente , Agricultura , Productos AgrícolasRESUMEN
Drought is a major constraint to plant growth and productivity worldwide and will aggravate as water availability becomes scarcer. Although elevated air [CO2] might mitigate some of these effects in plants, the mechanisms underlying the involved responses are poorly understood in woody economically important crops such as Coffea. This study analyzed transcriptome changes in Coffea canephora cv. CL153 and C. arabica cv. Icatu exposed to moderate (MWD) or severe water deficits (SWD) and grown under ambient (aCO2) or elevated (eCO2) air [CO2]. We found that changes in expression levels and regulatory pathways were barely affected by MWD, while the SWD condition led to a down-regulation of most differentially expressed genes (DEGs). eCO2 attenuated the impacts of drought in the transcripts of both genotypes but mostly in Icatu, in agreement with physiological and metabolic studies. A predominance of protective and reactive oxygen species (ROS)-scavenging-related genes, directly or indirectly associated with ABA signaling pathways, was found in Coffea responses, including genes involved in water deprivation and desiccation, such as protein phosphatases in Icatu, and aspartic proteases and dehydrins in CL153, whose expression was validated by qRT-PCR. The existence of a complex post-transcriptional regulatory mechanism appears to occur in Coffea explaining some apparent discrepancies between transcriptomic, proteomic, and physiological data in these genotypes.
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Coffea , Coffea/genética , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Carbono/metabolismo , Resistencia a la Sequía , Proteómica , Café/genética , Sequías , Agua/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
A 62-year-old woman was referred to Gastroenterology appointment due to severe iron deficiency anemia (5.9 g/dL), complaining of asthenia and requiring blood transfusion. The patient denied blood loss. Initial blood test showed a severe iron deficiency, with ferritin of 5ng/mL and transferrin saturation of 2.7%. Folic acid and vitamin B12 were normal. Upper gastroscopy and colonoscopy didn't show any lesions. Abdominopelvic CT and capsule endoscopy were, also, normal.
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Anemia Ferropénica , Hemorragia Gastrointestinal , Femenino , Humanos , Persona de Mediana Edad , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/complicaciones , Gastroscopía , Anemia Ferropénica/etiología , Colonoscopía/efectos adversos , Vitamina B 12 , Endoscopía Gastrointestinal/efectos adversosRESUMEN
BACKGROUND: Telemedicine use has increased significantly during the COVID-19 pandemic. It remains unclear if its rapid growth exacerbates disparities in healthcare access. We aimed to characterize telemedicine use among a large oncology population in the Deep South during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective cohort study was performed at the only National Cancer Institute designated-cancer center in Alabama March 2020 to December 2020. With a diverse (26.5% Black, 61% rural) population, this southeastern demographic uniquely reflects historically vulnerable populations. All non-procedural visits at the cancer center from March to December 2020 were included in this study excluding those with a department that had fewer than 100 visits during this time period. Patient and clinic level characteristics were analyzed using t-test and Chi-square to compare characteristics between visit types (in-person versus telemedicine, and video versus audio within telemedicine). Generalized estimating equations were used to identify independent factors associated with telemedicine use and type of telemedicine use. RESULTS: There were 50 519 visits and most were in-person (81.3%). Among telemedicine visits, most were phone based (58.3%). Black race and male sex predicted in-person visits. Telemedicine visits were less likely to have video among patients who were Black, older, male, publicly insured, and from lower income areas. CONCLUSIONS: Telemedicine use, specifically with video, is significantly lower among historically vulnerable populations. Understanding barriers to telemedicine use and preferred modalities of communication among different populations will help inform insurance reimbursement and interventions at different socioecological levels to ensure the continued evolution of telemedicine is equitable.
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COVID-19 , Neoplasias , Telemedicina , COVID-19/epidemiología , Humanos , Masculino , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias , Estudios RetrospectivosRESUMEN
The climate crisis is pushing the planet's tropical plants towards their limits [...].
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Cambio Climático , PlantasRESUMEN
Climate change is impacting locally adapted species such as the keystone tree species cork oak (Quercus suber L.). Quantifying the importance of environmental variables in explaining the species distribution can help build resilient populations in restoration projects and design forest management strategies. Using landscape genomics, we investigated the population structure and ecological adaptation of this tree species across the Mediterranean Basin. We applied genotyping by sequencing and derived 2,583 single nucleotide polymorphism markers genotyped from 81 individuals across 17 sites in the studied region. We implemented an approach based on the nearest neighbour haplotype 'coancestry' and uncovered a weak population structure along an east-west climatic gradient across the Mediterranean region. We identified genomic regions potentially involved in local adaptation and predicted differences in the genetic composition across the landscape under current and future climates. Variants associated with temperature and precipitation variables were detected, and we applied a nonlinear multivariate association method, gradient forest, to project these gene-environment relationships across space. The model allowed the identification of geographic areas within the western Mediterranean region most sensitive to climate change: south-western Iberia and northern Morocco. Our findings provide a preliminary assessment towards a potential management strategy for the conservation of cork oak in the Mediterranean Basin.
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Adaptación Biológica , Cambio Climático , Quercus , Ecosistema , Interacción Gen-Ambiente , Región Mediterránea , Modelos Estadísticos , Polimorfismo de Nucleótido SimpleRESUMEN
Understanding the effect of extreme temperatures and elevated air (CO2) is crucial for mitigating the impacts of the coffee industry. In this work, leaf transcriptomic changes were evaluated in the diploid C. canephora and its polyploid C. arabica, grown at 25 °C and at two supra-optimal temperatures (37 °C, 42 °C), under ambient (aCO2) or elevated air CO2 (eCO2). Both species expressed fewer genes as temperature rose, although a high number of differentially expressed genes (DEGs) were observed, especially at 42 °C. An enrichment analysis revealed that the two species reacted differently to the high temperatures but with an overall up-regulation of the photosynthetic machinery until 37 °C. Although eCO2 helped to release stress, 42 °C had a severe impact on both species. A total of 667 photosynthetic and biochemical related-DEGs were altered with high temperatures and eCO2, which may be used as key probe genes in future studies. This was mostly felt in C. arabica, where genes related to ribulose-bisphosphate carboxylase (RuBisCO) activity, chlorophyll a-b binding, and the reaction centres of photosystems I and II were down-regulated, especially under 42°C, regardless of CO2. Transcriptomic changes showed that both species were strongly affected by the highest temperature, although they can endure higher temperatures (37 °C) than previously assumed.
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Dióxido de Carbono/farmacología , Coffea/genética , Diploidia , Regulación de la Expresión Génica de las Plantas , Poliploidía , Temperatura , Transcriptoma/genética , Coffea/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Ontología de Genes , Genotipo , Fotosíntesis/efectos de los fármacos , Transcriptoma/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: It is accepted that contemporary allopolyploid species have originated recurrently, but very few cases have been documented using multiple natural formations of the same species. To extend our knowledge, we have investigated the multiple origins, genetic variation and structure of the allotetraploid grass Brachypodium hybridum with respect to its progenitor diploid species B. distachyon (D genome) and B. stacei (S genome). For this, our primary focus is the Iberian Peninsula, an evolutionary hotspot for the genus Brachypodium. METHODS: We analysed 342 B. hybridum individuals from 36 populations using ten nuclear SSR loci and two plastid loci. The B. hybridum genetic profiles were compared with those previously reported for B. stacei and B. distachyon. In addition, phylogenetic analysis of the plastid data was performed for a reduced subset of individuals. KEY RESULTS: The nuclear simple sequence repeat (SSR) genetic analysis detected medium to high genetic diversity, with a strong south-to-north genetic structure cline, and a high selfing rate in B. hybridum. Comparative genetic analysis showed a close relatedness of current B. hybridum D allelic profiles with those of B. distachyon, but a lack of similarity with those of B. stacei, suggesting another B. stacei source for the B. hybridum S alleles. Plastid analysis detected three different bidirectional allopolyploidization events: two involved distinct B. distachyon-like ancestors and one involved a B. stacei-like ancestor. The south-eastern Iberian Peninsula B. hybridum populations were more genetically diverse and could have originated from at least two hybridization events whereas north-eastern/north-western Iberian Peninsula B. hybridum populations were less diverse and may have derived from at least one hybridization event. CONCLUSIONS: The genetic and evolutionary evidence supports the plausible in situ origin of the south-eastern and northern Iberian Peninsula B. hybridum allopolyploids from their respective local B. distachyon and unknown B. stacei ancestors. The untapped multiple origins and genetic variation detected in these B. hybridum populations opens the way to future evolutionary analysis of allopolyploid formation and genomic dominance and expression in the B. hybridum-B. distachyon-B. stacei grass model complex.
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Brachypodium , Evolución Biológica , Diploidia , Variación Genética , FilogeniaRESUMEN
INTRODUCTION: Racial/ethnic disparities in surgical outcomes exist. Enhanced recovery programs (ERPs) have reduced some racial/ethnic disparities, but it remains unclear if disparities in experiences are also reduced. The purpose of this study was to use qualitative methods to better understand the surgical experience for African-American and Caucasian patients in the setting of an ERP. METHODS: Using purposeful sampling at a minority-serving institution, we recruited African-American and Caucasian patients who had undergone colorectal surgery under an ERP to six focus groups. Participants identified barriers and facilitators to a positive, or negative, surgical experience. Audio recordings were transcribed and analyzed using an indicative thematic approach with NVivo 10 software (QSR International). RESULTS: Forty-three patients (15 African-Americans and 28 Caucasians) participated in six focus groups. Six themes were identified by patients to be important in surgery: 1) knowledge about colorectal surgery, 2) obtaining information, 3) quality of information, 4) setting expectations about surgery, 5) following preoperative and postoperative instructions, and 6) confidence in surgery outcomes. For both racial/ethnic groups, patients felt that more information could have been provided, information should be given at their level of understanding, and trust in the physician made them feel confident in a positive outcome. African-American patients described experiences of having incorrect or no expectations on surgical outcomes, being provided inconsistent information, and feeling misled. African-Americans also described following instructions from family members and valued the importance of diet and exercise in recovery. CONCLUSIONS: African-American and Caucasian surgical patients have varied surgical experiences even under an ERP. All patients, however, valued the ability to obtain, process, and understand health information during the surgical process. These elements define "health literacy" and suggest the importance of providing health literacy-sensitive care in surgery.
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Recuperación Mejorada Después de la Cirugía , Conocimientos, Actitudes y Práctica en Salud/etnología , Disparidades en Atención de Salud/etnología , Complicaciones Posoperatorias/rehabilitación , Adulto , Negro o Afroamericano/psicología , Colon/cirugía , Femenino , Grupos Focales , Alfabetización en Salud , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Satisfacción del Paciente/etnología , Investigación Cualitativa , Recto/cirugía , Clase Social , Población Blanca/psicologíaRESUMEN
As atmospheric [CO2] continues to rise to unprecedented levels, understanding its impact on plants is imperative to improve crop performance and sustainability under future climate conditions. In this context, transcriptional changes promoted by elevated CO2 (eCO2) were studied in genotypes from the two major traded coffee species: the allopolyploid Coffea arabica (Icatu) and its diploid parent, C. canephora (CL153). While Icatu expressed more genes than CL153, a higher number of differentially expressed genes were found in CL153 as a response to eCO2. Although many genes were found to be commonly expressed by the two genotypes under eCO2, unique genes and pathways differed between them, with CL153 showing more enriched GO terms and metabolic pathways than Icatu. Divergent functional categories and significantly enriched pathways were found in these genotypes, which altogether supports contrasting responses to eCO2. A considerable number of genes linked to coffee physiological and biochemical responses were found to be affected by eCO2 with the significant upregulation of photosynthetic, antioxidant, and lipidic genes. This supports the absence of photosynthesis down-regulation and, therefore, the maintenance of increased photosynthetic potential promoted by eCO2 in these coffee genotypes.
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Dióxido de Carbono/metabolismo , Coffea/genética , Coffea/metabolismo , Regulación de la Expresión Génica de las Plantas , Transcriptoma , Presión del Aire , Biología Computacional/métodos , Perfilación de la Expresión Génica , Ontología de Genes , Genotipo , Anotación de Secuencia MolecularRESUMEN
Casuarina glauca displays high levels of salt tolerance, but very little is known about how this tree adapts to saline conditions. To understand the molecular basis of C. glauca response to salt stress, we have analyzed the proteome from branchlets of plants nodulated by nitrogen-fixing Frankia Thr bacteria (NOD+) and non-nodulated plants supplied with KNO3 (KNO3+), exposed to 0, 200, 400, and 600 mM NaCl. Proteins were identified by Short Gel, Long Gradient Liquid Chromatography coupled to Tandem Mass Spectrometry and quantified by Sequential Window Acquisition of All Theoretical Mass Spectra -Mass Spectrometry. 600 proteins were identified and 357 quantified. Differentially Expressed Proteins (DEPs) were multifunctional and mainly involved in Carbohydrate Metabolism, Cellular Processes, and Environmental Information Processing. The number of DEPs increased gradually with stress severity: (i) from 7 (200 mM NaCl) to 40 (600 mM NaCl) in KNO3+; and (ii) from 6 (200 mM NaCl) to 23 (600 mM NaCl) in NOD+. Protein-protein interaction analysis identified different interacting proteins involved in general metabolic pathways as well as in the biosynthesis of secondary metabolites with different response networks related to salt stress. Salt tolerance in C. glauca is related to a moderate impact on the photosynthetic machinery (one of the first and most important stress targets) as well as to an enhancement of the antioxidant status that maintains cellular homeostasis.
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Frankia/fisiología , Magnoliopsida/fisiología , Proteínas de Plantas/metabolismo , Nódulos de las Raíces de las Plantas/fisiología , Tolerancia a la Sal , Magnoliopsida/microbiología , Espectrometría de Masas/métodos , Proteoma/metabolismo , Proteómica/métodos , Nódulos de las Raíces de las Plantas/microbiología , Salinidad , SimbiosisRESUMEN
One hundred sequential, epidemiologically unrelated carbapenem-resistant- Acinetobacter baumannii isolates from 11 hospitals in 10 Argentine provinces were collected between January and August 2016. Genes coding for Ambler class D and B carbapenemases were investigated by PCR using specific primers. All isolates were typed using the 3-locus sequence typing and blaOXA-51-like sequence-based typing techniques. The blaOXA-23 gene was recovered in all isolates studied. The population of carbapenem-resistant- A. baumannii in Argentina was principally associated with ST1 (45%), ST25 (34%) and ST79 (15%). ST25 was recovered in all the regions studied and CC2 was not detected.
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Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/aislamiento & purificación , Proteínas Bacterianas/genética , Carbapenémicos/farmacología , Infección Hospitalaria/microbiología , Resistencia betalactámica , beta-Lactamasas/genética , Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/genética , Argentina/epidemiología , Infección Hospitalaria/epidemiología , HumanosRESUMEN
In order to describe the clinical and epidemiological characteristics of paracoccidioidomycosis, a descriptive study of all the cases diagnosed by the Clinical Microbiology Service at Dr. Julio C. Perrando hospital in the city of Resistencia (Chaco Province, Argentina) was conducted. Between 2011 and 2014, 46 cases were detected. In the period 2013-2014, an almost 4-fold increase in the incidence rate was detected. The chronic form of the disease was predominant with an average age of 53 years. Serological tests in 39 out of 46 patients were performed. In 15 of 39 patients, serological tests were the only diagnostic tool while in 4 patients with a microbiological diagnosis serological tests were non-reactive. In patients from endemic areas with non-specific infectious syndrome it is important to include paracoccidioidomycosis in the differential diagnosis and to apply all available diagnostic tools to reach a timely diagnosis and to reduce the long-term sequelae and their socio-economic impact.
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Paracoccidioidomicosis/diagnóstico , Paracoccidioidomicosis/epidemiología , Adulto , Anciano , Argentina/epidemiología , Femenino , Hospitales , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: We describe a female infant with Fragile-X syndrome, with a fully expanded FMR1 allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. CASE PRESENTATION: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. FMR1 mutation screening revealed a methylated full mutation and a normal but inactive FMR1 allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized FMR1 allele was found. No pathogenic variants were identified in the XIST promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. CONCLUSIONS: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases.