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1.
Am Nat ; 173(4): 488-98, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19239352

RESUMEN

All organisms alter their abiotic environment, but ecosystem engineers are species with abiotic effects that may have to be explicitly accounted for when making predictions about population and community dynamics. The goal of this analysis is to identify those conditions in which engineering leads to population dynamics that are qualitatively different than one would predict using models that incorporate only biotic interactions. We present a simple model coupling an ecosystem engineer and the abiotic environment. We assume that the engineer alters environmental conditions at a rate dependent on engineer density and that the environment decays back to original conditions at an exponential rate. We determine when the feedback to population dynamics through environmental state can lead to altered equilibrium densities, bistability, or runaway growth of the engineer population. The conditions leading to changes in dynamics, such as susceptibility of a system to engineering or alteration of density-dependent and density-independent controls, define cases in which the engineering concept is essential for ecological understanding.


Asunto(s)
Adaptación Biológica , Ecosistema , Modelos Biológicos , Dinámica Poblacional , Simulación por Computador
2.
Am Nat ; 162(2): 220-41, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12858266

RESUMEN

Hermaphroditism is typically associated with a sedentary existence, whereas dioecy is associated with mobility. This pattern is reflected within flowering plants, as dioecious species commonly possess traits that promote high dispersal. We investigated these associations with three population dynamics models (an individual-based simulation and two mathematical models, one deterministic and the other stochastic) that allowed us to examine competition for space between a hermaphroditic and dioecious species from different perspectives. The competing species are identical in every way but their sexual system. Separation of the sexes increases the variances of pollen import and seed dispersal for the dioecious species. These variances propagate through subsequent reproductive processes and ultimately reduce mean recruitment as a result of nonlinear averaging (Jensen's inequality). A dioecious species could overcome this disadvantage simply by producing more gametes than hermaphrodites; however, in line with the association with mobility, selection on dioecious species should also favor traits that reduce reproductive uncertainty, such as extensive dispersal.


Asunto(s)
Evolución Biológica , Conducta Competitiva , Trastornos del Desarrollo Sexual , Fenómenos Fisiológicos de las Plantas , Fertilización , Modelos Biológicos , Dinámica Poblacional , Reproducción/fisiología , Semillas/fisiología , Especificidad de la Especie , Procesos Estocásticos
3.
Prenat Diagn ; 21(10): 856-9, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11746129

RESUMEN

We report the occurrence of multiple acyl-CoA dehydrogenase deficiency (MADD) in two consecutive pregnancies in a young, Caucasian, non-consanguineous couple. In the first pregnancy, the maternal serum alpha-fetoprotein was elevated. A sonogram showed growth delay, cystic renal disease, and oligohydramnios; the parents decided to terminate the pregnancy. Postmortem examination confirmed the cystic renal disease and showed hepatic steatosis, raising the suspicion of a metabolic disorder. The diagnosis of MADD was made by immunoblot studies on cultured fibroblasts. In the subsequent pregnancy, a sonogram at 15 weeks' gestation showed an early growth delay but normal kidneys. The maternal serum and amniotic fluid concentrations of alpha-fetoprotein were elevated, and the amniotic fluid acylcarnitine profile was consistent with MADD. In vitro metabolic studies on cultured amniocytes confirmed the diagnosis. A follow-up sonogram showed cystic renal changes. These cases provide additional information regarding the evolution of renal changes in affected fetuses and show a relationship with elevated alpha-fetoprotein, which may be useful in counseling the couple at risk. MADD should be considered in the differential diagnosis of elevated alpha-fetoprotein and cystic renal disease. Early growth delay may be an additional feature.


Asunto(s)
Acil-CoA Deshidrogenasas/deficiencia , Carnitina/análogos & derivados , Enfermedades Renales Poliquísticas/diagnóstico por imagen , Diagnóstico Prenatal , alfa-Fetoproteínas/análisis , Acil-CoA Deshidrogenasa , Amniocentesis , Líquido Amniótico/química , Carnitina/análisis , Diagnóstico Diferencial , Hígado Graso/diagnóstico , Hígado Graso/etiología , Femenino , Enfermedades Fetales/diagnóstico , Retardo del Crecimiento Fetal/etiología , Edad Gestacional , Humanos , Oligohidramnios/diagnóstico por imagen , Enfermedades Renales Poliquísticas/etiología , Embarazo , Ultrasonografía Prenatal
4.
Theor Popul Biol ; 60(2): 93-106, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11703100

RESUMEN

Most single-species population models assume either that one sex dominates the growth dynamics (usually the female), or that the life cycles of the two sexes are identical; however, sexual differences in ontogenetic features can render this assumption invalid. Further, the interaction between sexes is necessarily nonlinear, and the dependence of dynamic behavior on sexual interactions can be complicated. Here we examine a two-sex population model, related to the well-known logistic model, with explicit sexual interactions. The model is bistable and, by the addition of diffusion, admits traveling wave solutions. Dominance of states via this spatial dynamic are examined. A simple condition for neutral dominance is obtained; sexual interactions inhibit the dominance of the nonzero population, making persistence more difficult.


Asunto(s)
Edad Gestacional , Reproducción , Razón de Masculinidad , Animales , Femenino , Modelos Logísticos , Masculino , Modelos Teóricos , Análisis Multivariante , Dinámica Poblacional , Estados Unidos
5.
Phys Rev E Stat Nonlin Soft Matter Phys ; 63(4 Pt 1): 041908, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11308878

RESUMEN

We study a model that gives rise to spatially inhomogeneous population densities in a system of host individuals subject to rare, randomly distributed disease events. For stationary hosts that disperse offspring over short distances, evolutionary dynamics can lead to persistent populations with a variety of spatial structures. A mean-field analysis is shown to account for the behavior observed in simulations of a one-dimensional system, where the evolutionarily stable state corresponds to the solution of a straightforward optimization problem. In two dimensions, evolution drives the system to a stable critical state that is less well understood.


Asunto(s)
Brotes de Enfermedades , Animales , Evolución Biológica , Modelos Biológicos , Modelos Teóricos , Fenómenos Físicos , Física , Dinámica Poblacional , Estadística como Asunto , Factores de Tiempo
6.
Theor Popul Biol ; 57(4): 377-90, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10900190

RESUMEN

This paper analyzes a consumer's adaptive feeding response to environmental gradients. We consider a consumer-resource system where resources are distributed among many discrete resource patches. Each consumer exhibits a feeding morphology allowing it to remove resources from a patch down to some threshold density (or level) before having to seek resources elsewhere. Assuming consumers trade off resource extraction with patch access and predation, we show that for a given environment there often exists a single evolutionarily stable feeding threshold and it is an evolutionary attractor. We then investigate how the population dynamics of the resource and the consumer change as the environment changes. Two cases are considered: (i) all consumers exhibit a fixed feeding threshold that is adaptive for an intermediate environment; and (ii) the consumer population adapts and adopts the evolutionarily stable feeding threshold associated with the current environment. In less harsh environments (i.e., environments where consumers experience a lower risk of predation, or environments where resource patches are more abundant) the adaptive consumer population is predicted to evolve so that resources within a patch are depleted to lower densities. We show that the change in consumer density due to environmental change can be rather different depending on whether or not the population can adapt. In some situations we observe that when the consumer's environment becomes harsher, the consumer population may increase in density before a rapid crash to extinction. This result has implications for monitoring and managing a population.


Asunto(s)
Adaptación Fisiológica , Ecosistema , Ambiente , Conducta Alimentaria , Modelos Biológicos , Animales , Evolución Biológica , Densidad de Población , Dinámica Poblacional
7.
Arch Pediatr Adolesc Med ; 154(3): 256-60, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10710023

RESUMEN

OBJECTIVE: To determine whether information collected during the National Resident Matching Program (NRMP) predicts clinical performance during residency. METHODS: Ten faculty members rated the overall quality of 69 pediatric house officers as clinicians. After rating by the faculty, folders were reviewed for absolute rank on the NRMP match list; relative ranking (where they ranked in their postgraduate year 1 [PGY-1] group); scores on part I of the National Board of Medical Examiners (NBME) examination; grades during medical school pediatrics and internal medicine rotations; membership in the Alpha Omega Alpha Medical Honor Society; scores of faculty interviews during intern application; scores on the pediatric in-service examination during PGY-1; and scores on the American Board of Pediatrics certification examination. RESULTS: There was substantial agreement among faculty raters as to the overall quality of the residents (agreement rate, 0.60; kappa = 0.50; P = .001). There was little correlation between faculty ratings and absolute (r = 0.19; P = .11) or relative (r = 0.20; P = .09) ranking on the NRMP match list. Individuals ranked in the top 10 of the match list had higher faculty ratings than did their peers (mean +/- SD, 3.66+/-1.22 vs. 3.0+/-1.27; P = .03), as did individuals ranked highest in their PGY-1 group (mean +/- SD, 3.88+/-1.45 vs. 3.04+/-1.24; P = .03). There was no correlation between faculty ratings and scores on part I of the NBME examination (r = 0.10; P = .49) or scores on the American Board of Pediatrics certification examination (r = 0.22; P = . 11). There were weak correlations between faculty ratings and scores of faculty interviews during the intern application process (r = 0.27; P = .02) and scores on the pediatric in-service examination during PGY-1 (r = 0.28; P = .02). There was no difference in faculty ratings of residents who were elected to Alpha Omega Alpha during medical school (mean +/- SD, 3.32+/-1.21) as compared with those who were not (mean +/- SD, 3.08+/-1.34) (P = .25). CONCLUSIONS: There is significant agreement among faculty raters about the clinical competence of pediatric residents. Medical school grades, performance on standardized examinations, interviews during the intern application process, and match-list ranking are not predictors of clinical performance during residency.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Internado y Residencia/estadística & datos numéricos , Pediatría/educación , Criterios de Admisión Escolar/estadística & datos numéricos , Adulto , Niño , Evaluación Educacional/estadística & datos numéricos , Femenino , Humanos , Masculino , Cuerpo Médico de Hospitales/estadística & datos numéricos , Consejos de Especialidades/estadística & datos numéricos , Virginia
8.
Am Nat ; 155(1): 83-100, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10657179

RESUMEN

A general consumer-resource model assuming discrete consumers and a continuously structured resource is examined. We study two foraging behaviors, which lead to fixed and flexible patch residence times, in conjunction with a simple consumer energetics model linking resource consumption, foraging behavior, and metabolic costs. Results indicate a single, evolutionarily stable foraging strategy for fixed and flexible foraging in a nonspatial environment, but flexible foraging in a spatial environment leads to consumer grouping, which affects the resource distribution such that no single foraging strategy can exclude all other strategies. This evolutionarily stable coexistence of multiple foraging strategies may help explain a dichotomous pattern observed in a wide variety of natural systems.

9.
Proc Biol Sci ; 266(1436): 2383-8, 1999 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-10643082

RESUMEN

How local interactions influence both population and evolutionary dynamics is currently a key topic in theoretical ecology. We use a 'well-mixed' analytical model and spatially explicit individual-based models to investigate a system where a population is subject to rare disturbance events. The disturbance can only propagate through regions of the population where the density of individuals is sufficiently high and individuals affected by the disturbance die shortly after. We find that populations where individuals are sessile often exhibit very different dynamic behaviour when compared to populations where individuals are mobile and spatially well mixed. When mutations are allowed which affect either offspring birth rates or mortality rates, the well-mixed populations always evolve to a state where a single disturbance event leads to extinction. Populations often persist substantially longer if individuals are sessile and they disperse their offspring locally. We also find that for sessile populations selection may favour short-lived individuals with limited offspring production. Population dynamics are found to be strongly influenced by the host characters that are evolving and the rate at which host variation is introduced into the system.


Asunto(s)
Modelos Teóricos , Dinámica Poblacional , Animales , Evolución Biológica , Desarrollo de la Planta
11.
Ann Neurol ; 44(1): 10-6, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9667588

RESUMEN

Mutations in the GTP-cyclohydrolase I (GCH) gene have been identified as a cause of two disorders: autosomal dominant hereditary progressive dystonia/dopa-responsive dystonia (HPD/DRD) and autosomal recessive GCH-deficient hyperphenylalaninemia (HPA). Detailed clinical descriptions and genetic analysis of patients with phenotypes intermediate between HPD/DRD (mild) and GCH-deficient HPA (severe) have not been reported. We conducted genomic DNA sequencing of the GCH gene in two patients (Cases 1 and 2) manifesting generalized dystonia responsive to levodopa and severe developmental motor delay. In the pedigree of Patient 1, there were HPD/DRD patients in three generations preceding the index case. Patients 1 and 2 were compound heterozygotes with maternally and paternally transmitted mutations in the coding region of the GCH gene. In both compound heterozygotes, tetrahydrobiopterin (BH4) levels in cerebrospinal fluid were lower than those in HPD/DRD. Administration of BH4, in addition to levodopa, further improved the symptomatology of Patient 1. Our data demonstrate a new phenotype of GCH deficiency associated with compound heterozygosity for GCH gene mutations and suggest the usefulness of combined BH4 and levodopa therapy for this disorder.


Asunto(s)
Distonía/genética , Mutación del Sistema de Lectura , Mutación Puntual , Adolescente , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/análisis , Biopterinas/administración & dosificación , Biopterinas/análogos & derivados , Biopterinas/líquido cefalorraquídeo , Niño , ADN/análisis , Quimioterapia Combinada , Distonía/líquido cefalorraquídeo , Distonía/tratamiento farmacológico , Femenino , Humanos , Levodopa/administración & dosificación , Masculino , Persona de Mediana Edad , Linaje
13.
Am Nat ; 152(5): 684-95, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18811343

RESUMEN

Given the predominance of outcrossing by angiosperms, large costs must often overwhelm the genetic benefit of selfing derived from contributing two haploid genomes to each off-spring rather than one. In addition to the well-studied genetic cost of inbreeding depression, selfing imposes a mating cost whenever self-pollination reduces opportunities for pollen export. Because self-pollination is a heterogeneous process, pollen discounting and its evolutionary consequences vary with pollination conditions. In this article we model self-pollination as comprising discounting and nondiscounting components, and we consider the consequences of this heterogeneity for outcross siring success. Aided by this depiction of pollination, we then compare previous theoretical representations of pollen discounting and consider their relative virtues. Finally, we consider conditions that would allow a population to be invaded by a variant with different pollination characteristics. This analysis exposes the pollination conditions implicit in standard results of mating system theory. It also identifies associations between four possible changes in pollination expected in different reproductive environments, including the incidence of positive or negative correlations between self-pollination and pollen export. These results emphasize the benefits of expanding the theory of plant reproduction to recognize explicitly when and how pollination mechanisms affect mating outcomes.

14.
Am Nat ; 151(2): 116-34, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18811412

RESUMEN

This work ties together two distinct modeling frameworks for population dynamics: an individual-based simulation and a set of coupled integrodifferential equations involving population densities. The simulation model represents an idealized predator-prey system formulated at the scale of discrete individuals, explicitly incorporating their mutual interactions, whereas the population-level framework is a generalized version of reaction-diffusion models that incorporate population densities coupled to one another by interaction rates. Here I use various combinations of long-range dispersal for both the offspring and adult stages of both prey and predator species, providing a broad range of spatial and temporal dynamics, to compare and contrast the two model frameworks. Taking the individual-based modeling results as given, two examinations of the reaction-dispersal model are made: linear stability analysis of the deterministic equations and direct numerical solution of the model equations. I also modify the numerical solution in two ways to account for the stochastic nature of individual-based processes, which include independent, local perturbations in population density and a minimum population density within integration cells, below which the population is set to zero. These modifications introduce new parameters into the population-level model, which I adjust to reproduce the individual-based model results. The individual-based model is then modified to minimize the effects of stochasticity, producing a match of the predictions from the numerical integration of the population-level model without stochasticity.

15.
Am Nat ; 151(1): 29-45, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18811422

RESUMEN

Many diseases have both sexual and nonsexual transmission routes, and closely related diseases often differ in their degree of sexual transmission. We investigate the evolution of transmission mode as a function of host social and mating structure using a model in which disease transmission is explicitly dependent on the numbers of sexual and nonsexual contacts (which are themselves a function of population density) and per-contact infection probabilities. Most generally, and in the absence of trade-offs between the degree of sexual transmission and effects on host fecundity and mortality, nonsexual transmission is favored above the social-sexual crossover point (the host density at which the number of nonsexual contacts exceeds the number of sexual contacts), while sexual transmission is favored below this point. When changes in allocation to the two transmission modes are accompanied by changes in mortality or fecundity, both mixed and pure transmission strategies can be favored. If invading genotypes differ substantially from resident genotypes, genetic polymorphism in transmission mode is possible. The evolutionary outcomes are predictable from a knowledge of the equilibrium population sizes in relation to the social-sexual crossover point. Our results also show that predictions about dynamic outcomes, based on rates of invasion for single pathogens into healthy populations, do not adequately describe the resulting disease prevalence nor predict the subsequent evolutionary dynamics; once invasion of a pathogen has occurred, the conditions for spread of a second pathogen are themselves altered. If the host is considered as a single resource, our results show that two pathogens may coexist on a single resource if they use that resource differentially and have differential feedbacks on resource abundance; such resource feedback effects may be present in other biological systems.

17.
Plast Reconstr Surg ; 100(1): 197-203; discussion 204-5, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9207677

RESUMEN

Silicone-containing breast implants have been used since 1963 for cosmetic augmentation and breast reconstruction. Currently, there is intense debate regarding the extent and mechanism of migration of silicone from the area of implant. The current study compares tissue distribution of organosilicon polymers between women with and without silicone breast implants to determine the extent of silicone migration from breast implants. Samples were collected at autopsy from 15 individuals with bilateral breast implants with no known history of chest trauma and from 14 age- and sex-matched controls. Capsule, breast, axillary lymph nodes, abdominal fat, liver, lung, and spleen were collected for analysis of organosilicon polymers by atomic absorption spectrometry and for examination by light microscopy. Blood was collected for analysis of rheumatoid factor and antinuclear antibodies. Silicone was observed microscopically in at least one capsule section from all implant cases and in at least one lymph node in 8 of 15 implant cases. Silicone was not observed in lymph nodes from control cases. Organosilicon polymers were extracted from tissue using heptane, and the silicon content of the extract was quantitated by atomic absorption spectrometry. Silicon was detected in all capsules; statistically significant increases of organosilicon polymers were measured in axillary lymph nodes, breast, and abdominal fat from individuals with silicone breast implants when compared with the nonimplant group. Measurable amounts of organosilicon polymers were found in tissues from the nonimplant group. Suitable blood specimens were analyzed for the presence of rheumatoid factor and antinuclear antibodies. All nine implant cases tested were negative for the presence of antinuclear antibodies. Three implant cases which were tested for rheumatoid factor also were negative. We conclude that organosilicon polymers routinely migrate from the site of breast implantation to regional tissues near the implant site. Tissues from nonimplant cases often contained measurable amounts of organosilicon polymers, and tissue distribution was variable within any single individual: this is consistent with the wide-spread use and form of organosilicon polymers.


Asunto(s)
Implantes de Mama , Mamoplastia , Compuestos de Organosilicio/farmacocinética , Adulto , Autopsia/estadística & datos numéricos , Implantes de Mama/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Compuestos de Organosilicio/análisis , Elastómeros de Silicona , Distribución Tisular
18.
Neurology ; 48(5): 1290-7, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9153460

RESUMEN

To determine if there is abnormal phenylalanine and biopterin metabolism in patients with dopa-responsive dystonia (DRD), we measured plasma levels of phenylalanine, tyrosine, biopterin, and neopterin at baseline, and 1, 2, 4, and 6 hours after an oral phenylalanine load (100 mg/kg). Seven adults with DRD, two severely affected children with DRD, and nine adult controls were studied. All patients had phenylalanine and tyrosine concentrations within the normal range at baseline. In the adult patients, phenylalanine levels were higher than in controls at 2, 4, and 6 hours post-load (p < 0.0005); tyrosine concentrations were lower than control levels at 1, 2, and 4 hours post-load (p < 0.05). Phenylalanine to tyrosine ratios were elevated in patients at all times post-load (p < 0.0005). Biopterin levels in the patients were decreased at baseline and 1, 2, and 4 hours post-load (p < 0.005). Pretreatment with tetrahydrobiopterin (7.5 mg/kg) normalized phenylalanine and tyrosine profiles in two adult patients. In the children with DRD, phenylalanine to tyrosine ratios were slightly elevated at baseline. Following phenylalanine loading, the phenylalanine profiles were similar to those seen in the adult patients but there was no elevation in plasma tyrosine. Baseline biopterin levels were lower in the children with DRD than in the adult patients or the controls and there was no increase in biopterin post-load. In both the children and adults with DRD, neopterin concentrations did not differ from control values at baseline or after phenylalanine load. The results are consistent with decreased liver phenylalanine hydroxylase activity due to defective synthesis of tetrahydrobiopterin in patients with DRD. The findings show that a phenylalanine load may be useful in the diagnosis of this disorder.


Asunto(s)
Dihidroxifenilalanina/uso terapéutico , Dopaminérgicos/uso terapéutico , Distonía/sangre , Distonía/tratamiento farmacológico , Fenilalanina , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Biopterinas/análogos & derivados , Biopterinas/sangre , Preescolar , Distonía/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neopterin , Concentración Osmolar , Fenilalanina/administración & dosificación , Fenilalanina/sangre , Factores de Tiempo , Tirosina/sangre
19.
Theor Popul Biol ; 50(3): 368-93, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9000495

RESUMEN

This paper further examines an individual-based model of a spatially distributed predator-prey population that demonstrates strong spatial structuring in contrast with predictions from its representative analytic formulation. Examination of a small, localized population reveals that extinctions due to demographic stochasticity dominate the dynamics. Local extinction dynamics produce wave pulses and the interactions of these wave pulses constitute global dynamics. The results motivate a population-level cell-based model with each cell representing a local population and parameterized by local extinction probabilities, rather than individual-based interaction rates. A detailed comparison of spatiotemporal plots from the two modelling frameworks shows that the population-level model captures the broad range of dynamics exhibited by the individual-based model. The agreement between these two complementary theoretical frameworks, one formulated at the level of individuals, the other at the level of populations, provides a mechanistic understanding of the dynamics.


Asunto(s)
Ecología , Genética de Población , Modelos Genéticos , Conducta Predatoria , Aglomeración , Densidad de Población , Reproducibilidad de los Resultados , Reproducción , Procesos Estocásticos
20.
J Clin Invest ; 98(4): 1021-7, 1996 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-8770875

RESUMEN

Individuals deficient in hepatic methionine adenosyltransferase (MAT) activity (MAT I/III deficiency) have been demonstrated to contain mutations in the gene (MATA1) that encodes the major hepatic forms, MAT I and III. MAT I/III deficiency is characterized by isolated persistent hypermethioninemia and, in some cases, unusual breath odor. Most individuals with isolated hypermethioninemia have been free of major clinical difficulties. Therefore a definitive diagnosis of MAT I/III deficiency, which requires hepatic biopsy, is not routinely made. However, two individuals with isolated hypermethioninemia have developed abnormal neurological problems, including brain demyelination, suggesting that MAT I/III deficiency can be deleterious. In the present study we have examined the MATA1 gene of eight hypermethioninemic individuals, including the two with demyelination of the brain. Mutations that abolish or reduce the MAT activity were detected in the MATA1 gene of all eight individuals. Both patients with demyelination are homozygous for mutations that alter the reading frame of the encoded protein such that the predicted MATalpha1 subunits are truncated and enzymatically inactive. The product of MAT, S-adenosylmethionine (AdoMet), is the major methyl donor for a large number of biologically important compounds including the two major myelin phospholipids, phosphatidylcholine and sphingomyelin. Both are synthesized primarily in the liver. Our findings demonstrate that isolated persistent hypermethioninemia is a marker of MAT I/III deficiency, and that complete lack of MAT I/III activity can lead to neurological abnormalities. Therefore, a DNA-based diagnosis should be performed for individuals with isolated hypermethioninemia to assess if therapy aimed at the prevention of neurological manifestations is warranted.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías/enzimología , Enfermedades Desmielinizantes/enzimología , Metionina Adenosiltransferasa/deficiencia , Metionina Adenosiltransferasa/genética , Metionina/metabolismo , Adolescente , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Encefalopatías/genética , Niño , Preescolar , Cromosomas Humanos Par 10 , Enfermedades Desmielinizantes/genética , Femenino , Genes , Humanos , Lactante , Masculino , Mutación Puntual , Polimorfismo Conformacional Retorcido-Simple
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