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1.
Int J Food Microbiol ; 415: 110631, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38402671

RESUMEN

Hanseniaspora vineae exhibits extraordinary positive oenological characteristics contributing to the aroma and texture of wines, especially by its ability to produce great concentrations of benzenoid and phenylpropanoid compounds compared with conventional Saccharomyces yeasts. Consequently, in practice, sequential inoculation of H. vineae and Saccharomyces cerevisiae allows to improve the aromatic quality of wines. In this work, we evaluated the impact on wine aroma produced by increasing the concentration of phenylalanine, the main amino acid precursor of phenylpropanoids and benzenoids. Fermentations were carried out using a Chardonnay grape juice containing 150 mg N/L yeast assimilable nitrogen. Fermentations were performed adding 60 mg/L of phenylalanine without any supplementary addition to the juice. Musts were inoculated sequentially using three different H. vineae strains isolated from Uruguayan vineyards and, after 96 h, S. cerevisiae was inoculated to complete the process. At the end of the fermentation, wine aromas were analysed by both gas chromatography-mass spectrometry and sensory evaluation through a panel of experts. Aromas derived from aromatic amino acids were differentially produced depending on the treatments. Sensory analysis revealed more floral character and greater aromatic complexity when compared with control fermentations without phenylalanine added. Moreover, fermentations performed in synthetic must with pure H. vineae revealed that even tyrosine can be used in absence of phenylalanine, and phenylalanine is not used by this yeast for the synthesis of tyrosine derivatives.


Asunto(s)
Hanseniaspora , Vino , Vino/análisis , Fermentación , Saccharomyces cerevisiae/metabolismo , Odorantes/análisis , Fenilalanina/análisis , Fenilalanina/metabolismo , Hanseniaspora/metabolismo , Tirosina/análisis , Tirosina/metabolismo
2.
Yeast ; 40(12): 640-650, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37997429

RESUMEN

Yeasts have been widely used as a model to better understand cell cycle mechanisms and how nutritional and genetic factors can impact cell cycle progression. While nitrogen scarcity is well known to modulate cell cycle progression, the relevance of nitrogen excess for microorganisms has been overlooked. In our previous work, we observed an absence of proper entry into the quiescent state in Hanseniaspora vineae and identified a potential link between this behavior and nitrogen availability. Furthermore, the Hanseniaspora genus has gained attention due to a significant loss of genes associated with DNA repair and cell cycle. Thus, the aim of our study was to investigate the effects of varying nitrogen concentrations on H. vineae's cell cycle progression. Our findings demonstrated that nitrogen excess, regardless of the source, disrupts cell cycle progression and induces G2/M arrest in H. vineae after reaching the stationary phase. Additionally, we observed a viability decline in H. vineae cells in an ammonium-dependent manner, accompanied by increased production of reactive oxygen species, mitochondrial hyperpolarization, intracellular acidification, and DNA fragmentation. Overall, our study highlights the events of the cell cycle arrest in H. vineae induced by nitrogen excess and attempts to elucidate the possible mechanism triggering this absence of proper entry into the quiescent state.


Asunto(s)
Hanseniaspora , Hanseniaspora/metabolismo , Apoptosis , Puntos de Control de la Fase G2 del Ciclo Celular , Línea Celular Tumoral , Nitrógeno/metabolismo
3.
FEMS Yeast Res ; 232023 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-36758966

RESUMEN

Apiculate yeasts belonging to the genus Hanseniaspora are predominant on grapes and other fruits. While some species, such as Hanseniaspora uvarum, are well known for their abundant presence in fruits, they are generally characterized by their detrimental effect on fermentation quality because the excessive production of acetic acid. However, the species Hanseniaspora vineae is adapted to fermentation and currently is considered as an enhancer of positive flavour and sensory complexity in foods. Since 2002, we have been isolating strains from this species and conducting winemaking processes with them. In parallel, we also characterized this species from genes to metabolites. In 2013, we sequenced the genomes of two H. vineae strains, being these the first apiculate yeast genomes determined. In the last 10 years, it has become possible to understand its biology, discovering very peculiar features compared to the conventional Saccharomyces yeasts, such as a natural and unique G2 cell cycle arrest or the elucidation of the mandelate pathway for benzenoids synthesis. All these characteristics contribute to phenotypes with proved interest from the biotechnological point of view for winemaking and the production of other foods.


Asunto(s)
Hanseniaspora , Vino , Hanseniaspora/genética , Fermentación , Vino/análisis , Levaduras/genética , Biología
4.
Curr Res Microb Sci ; 3: 100129, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35909624

RESUMEN

Yeasts of the genus Hanseniaspora gained notoriety in the last years due to their contribution to wine quality, and their loss of several genes, mainly related to DNA repair and cell cycle processes. Based on genomic data from many members of this genus, they have been classified in two well defined clades: the "faster-evolving linage" (FEL) and the "slower-evolving lineage" (SEL). In this context, we had detected that H. vineae exhibited a rapid loss of cell viability in some conditions during the stationary phase compared to H. uvarum and S. cerevisiae. The present work aimed to evaluate the viability and cell cycle progression of representatives of Hanseniaspora species along their growth in an aerobic and discontinuous system. Cell growth, viability and DNA content were determined by turbidity, Trypan Blue staining, and flow cytometry, respectively. Results showed that H. uvarum and H. opuntiae (representing FEL group), and H. osmophila (SEL group) exhibited a typical G1/G0 (1C DNA) arrest during the stationary phase, as S. cerevisiae. Conversely, the three strains studied here of H. vineae (SEL group) arrested at G2/M stages of cell cycle (2C DNA), and lost viability rapidly when enter the stationary phase. These results showed that H. vineae have a unique cell cycle behavior that will contribute as a new eukaryotic model for future studies of genetic determinants of yeast cell cycle control and progression.

5.
BMC Pregnancy Childbirth ; 21(1): 273, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33794829

RESUMEN

BACKGROUND: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. METHODS: We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. MAIN OUTCOME MEASURES: Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. RESULTS: Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32-3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11-2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43-8.94, p <  0.001) was also observed in positive mothers. CONCLUSION: This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.


Asunto(s)
COVID-19/epidemiología , Rotura Prematura de Membranas Fetales/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Adolescente , Adulto , Estudios de Casos y Controles , Cesárea/estadística & datos numéricos , Femenino , Edad Gestacional , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Trabajo de Parto Inducido/estadística & datos numéricos , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Embarazo , Estudios Prospectivos , SARS-CoV-2 , España/epidemiología , Adulto Joven
6.
Viruses ; 13(1)2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467629

RESUMEN

Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms.


Asunto(s)
Infecciones Asintomáticas/epidemiología , COVID-19/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , COVID-19/diagnóstico , Femenino , Humanos , Recién Nacido , Persona de Mediana Edad , Análisis Multivariante , Embarazo , Resultado del Embarazo , Mujeres Embarazadas , Estudios Prospectivos , SARS-CoV-2/aislamiento & purificación , España/epidemiología , Adulto Joven
7.
Yeast ; 37(9-10): 427-435, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32638443

RESUMEN

Benzenoids are compounds associated with floral and fruity flavours in flowers, fruits and leaves and present a role in hormonal signalling in plants. These molecules are produced by the phenyl ammonia lyase pathway. However, some yeasts can also synthesize them from aromatic amino acids using an alternative pathway that remains unknown. Hanseniaspora vineae can produce benzenoids at levels up to two orders of magnitude higher than Saccharomyces species, so it is a model microorganism for studying benzenoid biosynthesis pathways in yeast. According to their genomes, several enzymes have been proposed to be involved in a mandelate pathway similar to that described for some prokaryotic cells. Among them, the ARO10 gene product could present benzoylformate decarboxylase activity. This enzyme catalyses the decarboxylation of benzoylformate into benzaldehyde at the end of the mandelate pathway in benzyl alcohol formation. Two homologous genes of ARO10 were found in the two sequenced H. vineae strains. In this study, nine other H. vineae strains were analysed to detect the presence and per cent homology of ARO10 sequences by PCR using specific primers designed for this species. Also, the copy number of the genes was estimated by quantitative PCR. To verify the relation of ARO10 with the production of benzyl alcohol during fermentation, a deletion mutant in the ARO10 gene of Saccharomyces cerevisiae was used. The two HvARO10 paralogues were analysed and compared with other α-ketoacid decarboxylases at the sequence and structural level.


Asunto(s)
Derivados del Benceno/metabolismo , Vías Biosintéticas/genética , Hanseniaspora/genética , Piruvato Descarboxilasa/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transcriptoma , Benzaldehídos/metabolismo , Alcohol Bencilo/metabolismo , Fermentación , Hanseniaspora/metabolismo
9.
Appl Environ Microbiol ; 86(17)2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32561586

RESUMEN

Benzenoid-derived metabolites act as precursors for a wide variety of products involved in essential metabolic roles in eukaryotic cells. They are synthesized in plants and some fungi through the phenylalanine ammonia lyase (PAL) and tyrosine ammonia lyase (TAL) pathways. Ascomycete yeasts and animals both lack the capacity for PAL/TAL pathways, and metabolic reactions leading to benzenoid synthesis in these organisms have remained incompletely known for decades. Here, we show genomic, transcriptomic, and metabolomic evidence that yeasts use a mandelate pathway to synthesize benzenoids, with some similarities to pathways used by bacteria. We conducted feeding experiments using a synthetic fermentation medium that contained either 13C-phenylalanine or 13C-tyrosine, and, using methylbenzoylphosphonate (MBP) to inhibit benzoylformate decarboxylase, we were able to accumulate intracellular intermediates in the yeast Hanseniaspora vineae To further confirm this pathway, we tested in separate fermentation experiments three mutants with deletions in the key genes putatively proposed to form benzenoids (Saccharomyces cerevisiaearo10Δ, dld1Δ, and dld2Δ strains). Our results elucidate the mechanism of benzenoid synthesis in yeast through phenylpyruvate linked with the mandelate pathway to produce benzyl alcohol and 4-hydroxybenzaldehyde from the aromatic amino acids phenylalanine and tyrosine, as well as sugars. These results provide an explanation for the origin of the benzoquinone ring, 4-hydroxybenzoate, and suggest that Aro10p has benzoylformate and 4-hydroxybenzoylformate decarboxylase functions in yeast.IMPORTANCE We present here evidence of the existence of the mandelate pathway in yeast for the synthesis of benzenoids. The link between phenylpyruvate- and 4-hydroxyphenlypyruvate-derived compounds with the corresponding synthesis of benzaldehydes through benzoylformate decarboxylation is demonstrated. Hanseniaspora vineae was used in these studies because of its capacity to produce benzenoid derivatives at a level 2 orders of magnitude higher than that produced by Saccharomyces Contrary to what was hypothesized, neither ß-oxidation derivatives nor 4-coumaric acid is an intermediate in the synthesis of yeast benzenoids. Our results might offer an answer to the long-standing question of the origin of 4-hydroxybenzoate for the synthesis of Q10 in humans.


Asunto(s)
Derivados del Benceno/metabolismo , Hanseniaspora/metabolismo , Ácidos Mandélicos/metabolismo , Redes y Vías Metabólicas
11.
Front Microbiol ; 10: 2424, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31708896

RESUMEN

Melatonin is a bioactive compound that is present in fermented beverages and synthesized by yeast during alcoholic fermentation. Many studies have shown that melatonin interacts with some mammalian proteins, such as sirtuins or orphan receptor family proteins. The aim of this study was to determine the intracellular synthesis profile of melatonin in Saccharomyces cerevisiae and to identify the proteins that may interact with this molecule in yeast cells. Melatonin from fermentation samples was analyzed by liquid chromatography mass spectrometry, and proteins bound to melatonin were immunopurified by melatonin-IgG-Dynabeads. Melatonin was produced intracellularly in the lag phase of yeast growth and was exported to the extracellular media during the stationary phase. During this period, melatonin was bound to six proteins with molecular weights from 55 to 35 kDa. Sequence analysis showed that most proteins shared high levels of homology with glycolytic enzymes. An RNA-binding protein was also identified, the elongation alpha factor, which is related to mitochondria. This study reports for the first time the interaction of melatonin and proteins inside yeast cells. These results highlight the possible role of melatonin as a signal molecule and provide a new perspective for understanding its role in yeast.

16.
Int J Food Microbiol ; 289: 174-181, 2019 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-30253310

RESUMEN

During wine fermentation, yeasts produce metabolites that are known growth regulators. The relationship between certain higher alcohols derived from aromatic amino acid metabolism and yeast signalling has previously been reported. In the present work, tryptophol (TrpOH) or melatonin (MEL), which are putative growth regulators, were added to alcoholic fermentations. Fermentations were performed with three different inocula, combining Saccharomyces cerevisiae and four non-Saccharomyces yeast species, under two nitrogen conditions. The combinations tested were: (i) only S. cerevisiae; (ii) the mixture of four non-Saccharomyces species; and (iii) the combination of all five species together. The results revealed that the TrpOH and MEL addition caused changes in fermentation kinetics, viability and species distribution during fermentation, but it was dependent on the nitrogen present in the media and the composition of the inocula. Low nitrogen condition seemed to favour the presence of non-Saccharomyces species until mid-fermentation, although at the end of fermentation the imposition of Saccharomyces was higher in this condition. The presence of high concentrations of TrpOH resulted in limited growth and a delay in fermentation, noticeably significant in fermentations performed with S. cerevisiae inocula. These effects were reversed by the presence of non-Saccharomyces yeast in the medium. Low TrpOH concentration allowed faster fermentation with mixed non-Saccharomyces and Saccharomyces inocula. Moreover, in the absence of S. cerevisiae, a low concentration of TrpOH increased the presence of Torulaspora delbrueckii during fermentation with high nitrogen availability but not under low nitrogen conditions, when the population of S. bacillaris was higher than that in the control. The effects of MEL were particularly evident at the beginning and end of the process, primarily favouring the growth of non-Saccharomyces strains, especially the first hours after inoculation.


Asunto(s)
Fermentación/efectos de los fármacos , Indoles/farmacología , Melatonina/farmacología , Nitrógeno/metabolismo , Saccharomyces cerevisiae/efectos de los fármacos , Levaduras/efectos de los fármacos , Alcoholes/análisis , Aminoácidos Aromáticos/farmacología , Saccharomyces cerevisiae/metabolismo , Vino/análisis
17.
Appl Environ Microbiol ; 85(1)2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30366992

RESUMEN

Hanseniaspora is the main genus of the apiculate yeast group that represents approximately 70% of the grape-associated microflora. Hanseniaspora vineae is emerging as a promising species for quality wine production compared to other non-Saccharomyces species. Wines produced by H. vineae with Saccharomyces cerevisiae consistently exhibit more intense fruity flavors and complexity than wines produced by S. cerevisiae alone. In this work, genome sequencing, assembling, and phylogenetic analysis of two strains of H. vineae showed that it is a member of the Saccharomyces complex and it diverged before the whole-genome duplication (WGD) event from this clade. Specific flavor gene duplications and absences were identified in the H. vineae genome compared to 14 fully sequenced industrial S. cerevisiae genomes. The increased formation of 2-phenylethyl acetate and phenylpropanoids such as 2-phenylethyl and benzyl alcohols might be explained by gene duplications of H. vineae aromatic amino acid aminotransferases (ARO8 and ARO9) and phenylpyruvate decarboxylases (ARO10). Transcriptome and aroma profiles under fermentation conditions confirmed these genes were highly expressed at the beginning of stationary phase coupled to the production of their related compounds. The extremely high level of acetate esters produced by H. vineae compared to that by S. cerevisiae is consistent with the identification of six novel proteins with alcohol acetyltransferase (AATase) domains. The absence of the branched-chain amino acid transaminases (BAT2) and acyl coenzyme A (acyl-CoA)/ethanol O-acyltransferases (EEB1) genes correlates with H. vineae's reduced production of branched-chain higher alcohols, fatty acids, and ethyl esters, respectively. Our study provides sustenance for understanding and potentially utilizing genes that determine fermentation aromas.IMPORTANCE The huge diversity of non-Saccharomyces yeasts in grapes is dominated by the apiculate genus Hanseniaspora Two native strains of Hanseniaspora vineae applied to winemaking because of their high oenological potential in aroma and fermentation performance were selected to obtain high-quality genomes. Here, we present a phylogenetic analysis and the complete transcriptome and aroma metabolome of H. vineae during three fermentation steps. This species produced significantly richer flavor compound diversity than Saccharomyces, including benzenoids, phenylpropanoids, and acetate-derived compounds. The identification of six proteins, different from S. cerevisiae ATF, with diverse acetyltransferase domains in H. vineae offers a relevant source of native genetic variants for this enzymatic activity. The discovery of benzenoid synthesis capacity in H. vineae provides a new eukaryotic model to dilucidate an alternative pathway to that catalyzed by plants' phenylalanine lyases.


Asunto(s)
Genoma Fúngico , Hanseniaspora/genética , Gusto , Transcriptoma , Vino/análisis , Fermentación , Hanseniaspora/metabolismo
18.
Arch. bronconeumol. (Ed. impr.) ; 54(11): 551-558, nov. 2018. graf, tab
Artículo en Español | IBECS | ID: ibc-176699

RESUMEN

Introducción: Andalucía dispone de screening neonatal de fibrosis quística (SNFQ) desde mayo 2011, basado en doble determinación de tripsinógeno inmunorreactivo ([TIR] [TIR1/TIR2]). Si el screening es positivo realizamos un test del sudor y si es positivo o dudoso solicitamos genética. Objetivo: Analizar el SNFQ, basado en los resultados de los primeros 4,5 años. Material y método: Estudio descriptivo prospectivo de los neonatos sometidos a SNFQ. Se recogen los niveles de TIR, cloruro en sudor, mutaciones. Mediante SPSS12.0 se realizó análisis estadístico. Resultados: Desde mayo 2011 a diciembre 2016, 474.953 neonatos fueron sometidos a SNFQ. Mil ochenta y siete (0,23%) presentaron TIR2 elevado. Desde la implantación del SNFQ se diagnosticaron 73 casos con fibrosis quística; 60 de ellos fueron diagnosticados mediante un SNFQ positivo, mientras que 13 no. Concretamente un paciente comenzó con clínica clásica de fibrosis quística y se comprobó que no se había realizado el SNFQ por decisión paterna; los 12 restantes tuvieron un SNFQ negativo (falsos negativos). De estos, un paciente fue diagnosticado presintomáticamente al tener su hermano gemelo con SNFQ positivo; otro con cloruro en el límite alto de la normalidad se diagnosticó presintomáticamente mediante genética; 10 pacientes comenzaron clínicamente. Excluyendo los pacientes con íleo meconial, la sensibilidad y especificidad del programa de SNFQ asciende al 85,71 y 99,78% respectivamente. La incidencia de la enfermedad en Andalucía es de 1/6.506 recién nacidos vivos. Conclusión: Los presentes resultados nos permiten reflexionar sobre posibles áreas de mejoras adicionales del algoritmo del SNFQ, que debe pasar por la introducción de estudios genéticos para así aumentar la sensibilidad y disminuir los falsos positivos


Introduction: Cystic fibrosis neonatal screening (CFNS), based on double determination of immunoreactive trypsinogen ([IRT] [IRT1/IRT2]), has been available in Andalusia since May 2011. If screening is positive, a sweat test is performed, and if that is positive or inconclusive, genetic testing is requested. Objective: To analyze CFNS, based on results from the first 4.5 years of the program. Materials and methods: Prospective descriptive study of neonates undergoing CFNS. IRT levels, sweat chloride, and mutations were recorded. Statistical analysis was performed using SPSS 12.0. Results: Between May 2011 and December 2016, 474,953 neonates underwent CFNS. Of these, 1,087 (0.23%) had elevated IRT2. Since CFNS was introduced, 73 cases of cystic fibrosis were diagnosed; 60 were diagnosed by positive CFNS, and 13 were diagnosed by other means. In one case, the patient developed a typical clinical picture of cystic fibrosis, but had not undergone CFNS at the decision of the parents; the remaining 12 had a negative CFNS (false negatives). Of these, one patient was diagnosed before symptoms developed, as his twin brother had a positive CFNS result; another had chloride at the upper limit of normal, and was subsequently diagnosed with genetic testing before symptoms appeared; and 10 patients developed clinical signs and symptoms. Excluding patients with meconium ileus, sensitivity and specificity of the CFNS program were 85.71% and 99.78%, respectively. The incidence of the disease in Andalusia is 1/6,506 live births. Conclusion: These results are a basis for reflection on possible areas for improvement of the CFNS algorithm, and thought may be given to the introduction of genetic studies to increase sensitivity and reduce false positives


Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Fibrosis Quística/diagnóstico , Pruebas Genéticas/métodos , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Tripsinógeno/análisis , Fibrosis Quística/genética , Estudio Observacional , Sudor , Iontoforesis/métodos , Valor Predictivo de las Pruebas , Intervalos de Confianza
19.
Arch Bronconeumol (Engl Ed) ; 54(11): 551-558, 2018 Nov.
Artículo en Inglés, Español | MEDLINE | ID: mdl-29983195

RESUMEN

INTRODUCTION: Cystic fibrosis neonatal screening (CFNS), based on double determination of immunoreactive trypsinogen ([IRT] [IRT1/IRT2]), has been available in Andalusia since May 2011. If screening is positive, a sweat test is performed, and if that is positive or inconclusive, genetic testing is requested. OBJECTIVE: To analyze CFNS, based on results from the first 4.5 years of the program. MATERIALS AND METHODS: Prospective descriptive study of neonates undergoing CFNS. IRT levels, sweat chloride, and mutations were recorded. Statistical analysis was performed using SPSS 12.0. RESULTS: Between May 2011 and December 2016, 474,953 neonates underwent CFNS. Of these, 1,087 (0.23%) had elevated IRT2. Since CFNS was introduced, 73 cases of cystic fibrosis were diagnosed; 60 were diagnosed by positive CFNS, and 13 were diagnosed by other means. In one case, the patient developed a typical clinical picture of cystic fibrosis, but had not undergone CFNS at the decision of the parents; the remaining 12 had a negative CFNS (false negatives). Of these, one patient was diagnosed before symptoms developed, as his twin brother had a positive CFNS result; another had chloride at the upper limit of normal, and was subsequently diagnosed with genetic testing before symptoms appeared; and 10 patients developed clinical signs and symptoms. Excluding patients with meconium ileus, sensitivity and specificity of the CFNS program were 85.71% and 99.78%, respectively. The incidence of the disease in Andalusia is 1/6,506 live births. CONCLUSION: These results are a basis for reflection on possible areas for improvement of the CFNS algorithm, and thought may be given to the introduction of genetic studies to increase sensitivity and reduce false positives.


Asunto(s)
Fibrosis Quística/diagnóstico , Tamizaje Neonatal , Algoritmos , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , España , Factores de Tiempo
20.
Sci Rep ; 7: 46175, 2017 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-28397860

RESUMEN

Congenital glaucoma (CG) is a heterogeneous, inherited and severe optical neuropathy that originates from maldevelopment of the anterior segment of the eye. To identify new disease genes, we performed whole-exome sequencing of 26 unrelated CG patients. In one patient we identified two rare, recessive and hypermorphic coding variants in GPATCH3, a gene of unidentified function, and 5% of a second group of 170 unrelated CG patients carried rare variants in this gene. The recombinant GPATCH3 protein activated in vitro the proximal promoter of CXCR4, a gene involved in embryo neural crest cell migration. The GPATCH3 protein was detected in human tissues relevant to glaucoma (e.g., ciliary body). This gene was expressed in the dermis, skeletal muscles, periocular mesenchymal-like cells and corneal endothelium of early zebrafish embryos. Morpholino-mediated knockdown and transient overexpression of gpatch3 led to varying degrees of goniodysgenesis and ocular and craniofacial abnormalities, recapitulating some of the features of zebrafish embryos deficient in the glaucoma-related genes pitx2 and foxc1. In conclusion, our data suggest the existence of high genetic heterogeneity in CG and provide evidence for the role of GPATCH3 in this disease. We also show that GPATCH3 is a new gene involved in ocular and craniofacial development.


Asunto(s)
Proteínas Portadoras/genética , Secuenciación del Exoma , Ojo/embriología , Cara/embriología , Glaucoma/congénito , Glaucoma/genética , Mutación/genética , Cráneo/embriología , Animales , Segregación Cromosómica/genética , Embrión no Mamífero/metabolismo , Familia , Femenino , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Persona de Mediana Edad , Especificidad de Órganos/genética , Linaje , Fenotipo , Regiones Promotoras Genéticas/genética , Receptores CXCR4/genética , Fracciones Subcelulares/metabolismo , Activación Transcripcional/genética , Pez Cebra/embriología , Pez Cebra/genética
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