Benjamin Gomez | Instituto Nacional de Salud (original) (raw)
Papers by Benjamin Gomez
Genetic counseling (Geneva, Switzerland)
In this report we present the analysis of a sporadic case of DMD and his family. In the present c... more In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.
Pithed rat model is a useful and versatile preparation for studying the cardiovascular effects of... more Pithed rat model is a useful and versatile preparation for studying the cardiovascular effects of a wide range of drugs and their mechanism of action. This preparation allows to exclude central mechanisms (for example, baroreceptor reflex), which can modify considerably the effects of drugs on peripheral resistance or heart rate. Moreover, the sympathetic outflow can be selectively stimulated in this model and the effects of several drugs on sympathetic outflow can be determined. We have shown in this experimental model that several receptors (5-hydroxytryptamine receptors, alpha2-adrenoceptors, among others) can inhibit the cardiac and/or the vasopressor sympathetic outflow as well as the non-adrenergic noncholinergic vasodepressor sensory outflow. In addition, the effects of several new drugs on the systemic blood pressure or the heart rate can be determined in this experimental model. Thus, potential antihypertensive drugs can be detected by using this model. However, one of the ...
Molecules, 2015
M.A.A.-S.); ialvarez@ciatej.mx (I.A.-M.)
Genetic counseling (Geneva, Switzerland), 2014
Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding result... more Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to e...
International Journal of Molecular Sciences, 2015
Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dys... more Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.
![Research paper thumbnail of [Diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy: experience and recommendations for Mexico. Administración del Patrimonio de la Beneficencia Pública. Asociación de Distrofia Muscular de Occidente]](https://attachments.academia-assets.com/39757748/thumbnails/1.jpg)
](Revista de neurologia, Jan 16, 2013
Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3... more Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The long-term steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwi...
Parasitology International, 2011
Chinchilla laniger has been reported as an experimental definitive host for Taenia solium; howeve... more Chinchilla laniger has been reported as an experimental definitive host for Taenia solium; however no information about its suitability and yield of gravid tapeworm proglottids containing viable and infective eggs has been published. In total 55 outbred female chinchillas were infected with 4 cysticerci each; hosts were immunodeppressed with 6 or 8 mg of methyl-prednisolone acetate every 14 days starting the day of infection and their discomfort was followed. Kinetics of coproantigen ELISA or expelled proglottids was used to define the infection status. Efficiency of tapeworm establishment was 21% and of parasite gravidity was 8%; chinchillas showed some degree of suffering along the infection. Viability of eggs obtained from gravid proglottids was tested comparing methods previously published, our results showed 62% viability with propidium iodide, 54% with trypan blue, 34% with neutral red, 30% by oncosphere activation and 7% with bromide 3-(4,5-dimetil-tiazol-2-il)-2,5-difenil-tetrazolio (MTT) reduction; no statistical differences were obtained between most techniques, except activation. Four piglets were infected with 50,000 eggs each, necropsy was performed 3 months later and, after counting the number of cysticerci recovered, the percentage of infection was similar to data obtained with T. solium eggs recovered from humans. Our results demonstrate that the experimental model of T. solium taeniasis in C. laniger is a good alternative for providing eggs and adult tapeworms to be used in different types of experiments; optimization of the model probably depends on the use of inbred hosts and on the reduction of infected animals' suffering.
Muscle & Nerve, 2012
Introduction: The muscular dystrophies (MDs) result from perturbations in the myofibers. These al... more Introduction: The muscular dystrophies (MDs) result from perturbations in the myofibers. These alterations are induced in part by mechanical stress due to membrane cell fragility, disturbances in mechanotransduction pathways, muscle cell physiology, and metabolism. Methods: We analyzed 290 biopsies of patients with a clinical diagnosis of muscular dystrophy. Using immunofluorescence staining, we searched for primary and secondary deficiencies of 12 different proteins, including membrane, costamere, cytoskeletal, and nuclear proteins. In addition, we analyzed calpain-3 by immunoblot. Results: We identified 212 patients with varying degrees of protein deficiencies, including dystrophin, sarcoglycans, dysferlin, caveolin-3, calpain-3, emerin, and merosin. Moreover, 78 biopsies showed normal expression of all investigated muscle proteins. The frequency rates of protein deficiencies were as follows: 52.36% dystrophinopathies; 18.40% dysferlinopathies; 14.15% sarcoglycanopathies; 11.32% calpainopathies; 1.89% merosinopathies; 1.42% caveolinopathies; and 0.47% emerinopathies. Deficiencies in lamin A/C and telethonin were not detected. Conclusion: We have described the frequency of common muscular dystrophies in Mexico.
Journal of Genetics, 2014
López-Hernández L. B., Gómez-Díaz B., Bahena-Martínez E., Neri-Gómez T., Camacho-Molina A., Ruano... more López-Hernández L. B., Gómez-Díaz B., Bahena-Martínez E., Neri-Gómez T., Camacho-Molina A., Ruano-Calderón L. A. , García S. and Coral-Vázquez R. M. 2014 A novel noncontiguous duplication in the DMD gene escapes the 'reading-frame rule'. J. Genet. 93, 225-229] Some authors have recognized subphenotypes different from DMD/BMD. Desguerre et al. defined classic DMD
Genetic Testing, 2007
Dysferlin protein (DYSF) is a ferlin family member found in sarcolemma and is involved in membran... more Dysferlin protein (DYSF) is a ferlin family member found in sarcolemma and is involved in membrane repair, muscle differentiation, membrane fusion, etc. The deficiency of DYSF due to mutations is associated with different pathologic phenotypes including the autosomal recessive limb-girdle type 2B phenotype (LGMD2B), a distal anterior compartment myopathy (DMAT), and the Miyoshi myopathy (MM). In this study, we determined a missense mutation c.4253GϾA on the DYSF gene in a Mexican family from an endogamic population. This mutation was assumed to be the cause of dystrophy because only homozygous individuals of the family manifest a clinical phenotype. Structural implications caused by G/D substitution at amino acid position 1418 are discussed in terms of potential importance of the dysferlin neighboring sequence.
European Journal of Pharmacology, 2009
This study analysed the inhibition produced by the agonists moxonidine (imidazoline I 1 receptors... more This study analysed the inhibition produced by the agonists moxonidine (imidazoline I 1 receptors N α 2adrenoceptors) and agmatine (endogenous ligand of imidazoline I 1 /I 2 receptors), using B-HT 933 (6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepin-2-amine dihydrochloride; α 2 -adrenoceptors) for comparison, on the rat cardioaccelerator sympathetic outflow. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or noradrenaline produced, respectively, frequency-dependent and dose-dependent tachycardic responses. I.v. continuous infusions of moxonidine (3 and 10 µg/kg min), agmatine (1000 and 3000 µg/kg min) and B-HT 933 (30 and 100 µg/kg min) inhibited the tachycardic responses to sympathetic stimulation, but not those to noradrenaline. The cardiac sympatho-inhibition by either moxonidine (3 µg/kg min) or B-HT 933 (30 µg/kg min) was not modified by i.v. injections of saline or the antagonists AGN192403 [(±)-2-endo-Amino-3-exoisopropylbicyclo[2.2.1]heptane hydrochloride; 3000 µg/kg; imidazoline I 1 receptors] or BU224 (2-(4,5dihydroimidazol-2-yl)quinoline hydrochloride; 300 µg/kg; imidazoline I 2 receptors) and abolished by rauwolscine (300 µg/kg; α 2 -adrenoceptors). At the same doses of these compounds, the sympathoinhibition to moxonidine (10 µg/kg min) and agmatine (1000 µg/kg min) was: (1) not modified by saline, AGN192403 or BU224; (2) partially blocked by rauwolscine or the combination of rauwolscine plus BU224; and (3) abolished by the combination of rauwolscine plus AGN192403. These results demonstrate that the cardiac sympatho-inhibition to: (1) 3 µg/kg min moxonidine or 30 µg/kg min B-HT 933 involves α 2adrenoceptors; and (2) 10 µg/kg min moxonidine or 1000 µg/kg min agmatine involves α 2 -adrenoceptors and imidazoline I 1 receptors.
Genetic counseling (Geneva, Switzerland)
In this report we present the analysis of a sporadic case of DMD and his family. In the present c... more In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.
Pithed rat model is a useful and versatile preparation for studying the cardiovascular effects of... more Pithed rat model is a useful and versatile preparation for studying the cardiovascular effects of a wide range of drugs and their mechanism of action. This preparation allows to exclude central mechanisms (for example, baroreceptor reflex), which can modify considerably the effects of drugs on peripheral resistance or heart rate. Moreover, the sympathetic outflow can be selectively stimulated in this model and the effects of several drugs on sympathetic outflow can be determined. We have shown in this experimental model that several receptors (5-hydroxytryptamine receptors, alpha2-adrenoceptors, among others) can inhibit the cardiac and/or the vasopressor sympathetic outflow as well as the non-adrenergic noncholinergic vasodepressor sensory outflow. In addition, the effects of several new drugs on the systemic blood pressure or the heart rate can be determined in this experimental model. Thus, potential antihypertensive drugs can be detected by using this model. However, one of the ...
Molecules, 2015
M.A.A.-S.); ialvarez@ciatej.mx (I.A.-M.)
Genetic counseling (Geneva, Switzerland), 2014
Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding result... more Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to e...
International Journal of Molecular Sciences, 2015
Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dys... more Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.
Revista de neurologia, Jan 16, 2013
Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3... more Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The long-term steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwi...
Parasitology International, 2011
Chinchilla laniger has been reported as an experimental definitive host for Taenia solium; howeve... more Chinchilla laniger has been reported as an experimental definitive host for Taenia solium; however no information about its suitability and yield of gravid tapeworm proglottids containing viable and infective eggs has been published. In total 55 outbred female chinchillas were infected with 4 cysticerci each; hosts were immunodeppressed with 6 or 8 mg of methyl-prednisolone acetate every 14 days starting the day of infection and their discomfort was followed. Kinetics of coproantigen ELISA or expelled proglottids was used to define the infection status. Efficiency of tapeworm establishment was 21% and of parasite gravidity was 8%; chinchillas showed some degree of suffering along the infection. Viability of eggs obtained from gravid proglottids was tested comparing methods previously published, our results showed 62% viability with propidium iodide, 54% with trypan blue, 34% with neutral red, 30% by oncosphere activation and 7% with bromide 3-(4,5-dimetil-tiazol-2-il)-2,5-difenil-tetrazolio (MTT) reduction; no statistical differences were obtained between most techniques, except activation. Four piglets were infected with 50,000 eggs each, necropsy was performed 3 months later and, after counting the number of cysticerci recovered, the percentage of infection was similar to data obtained with T. solium eggs recovered from humans. Our results demonstrate that the experimental model of T. solium taeniasis in C. laniger is a good alternative for providing eggs and adult tapeworms to be used in different types of experiments; optimization of the model probably depends on the use of inbred hosts and on the reduction of infected animals' suffering.
Muscle & Nerve, 2012
Introduction: The muscular dystrophies (MDs) result from perturbations in the myofibers. These al... more Introduction: The muscular dystrophies (MDs) result from perturbations in the myofibers. These alterations are induced in part by mechanical stress due to membrane cell fragility, disturbances in mechanotransduction pathways, muscle cell physiology, and metabolism. Methods: We analyzed 290 biopsies of patients with a clinical diagnosis of muscular dystrophy. Using immunofluorescence staining, we searched for primary and secondary deficiencies of 12 different proteins, including membrane, costamere, cytoskeletal, and nuclear proteins. In addition, we analyzed calpain-3 by immunoblot. Results: We identified 212 patients with varying degrees of protein deficiencies, including dystrophin, sarcoglycans, dysferlin, caveolin-3, calpain-3, emerin, and merosin. Moreover, 78 biopsies showed normal expression of all investigated muscle proteins. The frequency rates of protein deficiencies were as follows: 52.36% dystrophinopathies; 18.40% dysferlinopathies; 14.15% sarcoglycanopathies; 11.32% calpainopathies; 1.89% merosinopathies; 1.42% caveolinopathies; and 0.47% emerinopathies. Deficiencies in lamin A/C and telethonin were not detected. Conclusion: We have described the frequency of common muscular dystrophies in Mexico.
Journal of Genetics, 2014
López-Hernández L. B., Gómez-Díaz B., Bahena-Martínez E., Neri-Gómez T., Camacho-Molina A., Ruano... more López-Hernández L. B., Gómez-Díaz B., Bahena-Martínez E., Neri-Gómez T., Camacho-Molina A., Ruano-Calderón L. A. , García S. and Coral-Vázquez R. M. 2014 A novel noncontiguous duplication in the DMD gene escapes the 'reading-frame rule'. J. Genet. 93, 225-229] Some authors have recognized subphenotypes different from DMD/BMD. Desguerre et al. defined classic DMD
Genetic Testing, 2007
Dysferlin protein (DYSF) is a ferlin family member found in sarcolemma and is involved in membran... more Dysferlin protein (DYSF) is a ferlin family member found in sarcolemma and is involved in membrane repair, muscle differentiation, membrane fusion, etc. The deficiency of DYSF due to mutations is associated with different pathologic phenotypes including the autosomal recessive limb-girdle type 2B phenotype (LGMD2B), a distal anterior compartment myopathy (DMAT), and the Miyoshi myopathy (MM). In this study, we determined a missense mutation c.4253GϾA on the DYSF gene in a Mexican family from an endogamic population. This mutation was assumed to be the cause of dystrophy because only homozygous individuals of the family manifest a clinical phenotype. Structural implications caused by G/D substitution at amino acid position 1418 are discussed in terms of potential importance of the dysferlin neighboring sequence.
European Journal of Pharmacology, 2009
This study analysed the inhibition produced by the agonists moxonidine (imidazoline I 1 receptors... more This study analysed the inhibition produced by the agonists moxonidine (imidazoline I 1 receptors N α 2adrenoceptors) and agmatine (endogenous ligand of imidazoline I 1 /I 2 receptors), using B-HT 933 (6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepin-2-amine dihydrochloride; α 2 -adrenoceptors) for comparison, on the rat cardioaccelerator sympathetic outflow. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or noradrenaline produced, respectively, frequency-dependent and dose-dependent tachycardic responses. I.v. continuous infusions of moxonidine (3 and 10 µg/kg min), agmatine (1000 and 3000 µg/kg min) and B-HT 933 (30 and 100 µg/kg min) inhibited the tachycardic responses to sympathetic stimulation, but not those to noradrenaline. The cardiac sympatho-inhibition by either moxonidine (3 µg/kg min) or B-HT 933 (30 µg/kg min) was not modified by i.v. injections of saline or the antagonists AGN192403 [(±)-2-endo-Amino-3-exoisopropylbicyclo[2.2.1]heptane hydrochloride; 3000 µg/kg; imidazoline I 1 receptors] or BU224 (2-(4,5dihydroimidazol-2-yl)quinoline hydrochloride; 300 µg/kg; imidazoline I 2 receptors) and abolished by rauwolscine (300 µg/kg; α 2 -adrenoceptors). At the same doses of these compounds, the sympathoinhibition to moxonidine (10 µg/kg min) and agmatine (1000 µg/kg min) was: (1) not modified by saline, AGN192403 or BU224; (2) partially blocked by rauwolscine or the combination of rauwolscine plus BU224; and (3) abolished by the combination of rauwolscine plus AGN192403. These results demonstrate that the cardiac sympatho-inhibition to: (1) 3 µg/kg min moxonidine or 30 µg/kg min B-HT 933 involves α 2adrenoceptors; and (2) 10 µg/kg min moxonidine or 1000 µg/kg min agmatine involves α 2 -adrenoceptors and imidazoline I 1 receptors.