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1.
Gene Ther ; 24(9): 529-533, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28644430

RESUMEN

Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy. The advent of the first tailored molecular therapy for SMA, based on modulating the splicing behaviour of the SMN2 gene provides, for the first time, a treatment which alters the natural history of motor neuron degeneration. Here we consider how this will change the landscape for diagnosis, clinical management and future therapeutic trials in SMA, as well as the implications for the molecular therapy of other neurological diseases.


Asunto(s)
Terapia Genética/métodos , Atrofia Muscular Espinal/terapia , Animales , Pruebas Genéticas/métodos , Terapia Genética/tendencias , Humanos , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Proteína 1 para la Supervivencia de la Neurona Motora/metabolismo , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Proteína 2 para la Supervivencia de la Neurona Motora/metabolismo
2.
Clin Genet ; 85(5): 470-5, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-23799925

RESUMEN

Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in the survival motor neuron1 gene (SMN1). Global carrier frequency is around 1 in 50 and carrier detection is crucial to define couples at risk to have SMA offspring. Most SMA carriers have one SMN1 copy and are currently detected using quantitative methods. A few, however, have two SMN1 genes in cis (2/0 carriers), complicating carrier diagnosis in SMA. We analyzed our experience in detecting 2/0 carriers from a cohort of 1562 individuals, including SMA parents, SMA relatives, and unrelated individuals of the general population. Interestingly, in three couples who had an SMA child, both the parents had two SMN1 copies. Families of this type have not been previously reported. Our results emphasize the importance of performing a detailed carrier study in SMA parents with two SMN1 copies. Expanding the analysis to other key family members might confirm potential 2/0 carriers. Finally, when a partner of a known carrier presents two SMN1 copies, the study of both parents will provide a more accurate diagnosis, thus optimizing genetic counseling.


Asunto(s)
Duplicación de Gen/genética , Tamización de Portadores Genéticos , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Niño , Femenino , Asesoramiento Genético , Heterocigoto , Humanos , Masculino , Atrofia Muscular Espinal/fisiopatología , Mutación , Diagnóstico Prenatal
3.
Haemophilia ; 18(5): 708-13, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22621702

RESUMEN

We performed molecular analysis of the factor 8 gene (F8) in 272 unrelated Spanish patients with haemophilia A (HA) and detected a mutation by routine analysis in 267 of them (98.1%). No mutation was detected in the remaining five patients despite clinical and laboratory confirmation of HA. The aim is to describe the molecular alterations in F8 discovered by gene dosage methodologies in three of these patients. For methodology, F8 sequencing, intragenic marker analysis, multiplex ligation-dependent probe amplification and quantitative real time-PCR were followed. One patient had Klinefelter syndrome (47,XXY) and a large deletion spanning exons 1-12 masked by the other F8 allele; the second patient showed a large duplication spanning exons 2-10 and the third patient revealed a non-contiguous double duplication of exons 14 and 23-25. The remaining two patients had mild HA and dosage results were normal. The application of gene dosage methods is useful to define haemophilic patients in whom mutations are not detected using other routine methods. Nevertheless, in a small percentage of patients (<1%), no molecular pathology can be identified after testing several genetic methodologies.


Asunto(s)
Factor VIII/genética , Dosificación de Gen , Hemofilia A/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Análisis Mutacional de ADN , Exones , Duplicación de Gen , Hemofilia A/complicaciones , Humanos , Síndrome de Klinefelter/complicaciones , Síndrome de Klinefelter/genética , Masculino , Reacción en Cadena de la Polimerasa Multiplex , Linaje , Eliminación de Secuencia , España
4.
J Med Genet ; 47(9): 640-2, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20577007

RESUMEN

Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA). A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c.859G>C variant in SMN2 has been recently reported as a positive disease modifier. We identified the variant in 10 unrelated chronic SMA patients with a wide spectrum of phenotypes ranging from type II patients who can only sit to adult walkers. Haplotype analysis strongly suggests that the variant originated from a common ancestor. Our results confirm that the c.859G>C variant is a milder SMN2 allele and predict a direct correlation between SMN activity and phenotypic severity.


Asunto(s)
Atrofia Muscular Espinal/clasificación , Atrofia Muscular Espinal/genética , Mutación/genética , Filogenia , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Adolescente , Niño , Preescolar , Femenino , Homocigoto , Humanos , Masculino , Fenotipo , España , Proteína 2 para la Supervivencia de la Neurona Motora/clasificación
5.
Eur J Neurol ; 17(1): 160-2, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19538222

RESUMEN

BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder. Carrier frequency studies of SMA have been reported for various populations. Although no large-scale population-based studies of SMA have been performed in Iran, previous estimates have indicated that the incidence of autosomal recessive disorder partly because of the high prevalence of consanguineous marriage is much higher in the Iranian population than in other populations. METHODS: In this study, we used a reliable and highly sensitive quantitative real-time PCR assay with SYBR green I dye to detect the copy number of the SMN1 gene to determine the carrier frequency of SMA in 200 healthy unrelated, non-consanguineous couples from different part of Iran. RESULTS: To validate the method in our samples, we determined the relative quantification (RQ) of patients with homozygous deletion (0.00) and hemyzygous carriers (0.29-0.55). The RQ in 10 of 200 normal individuals were within the carrier range of 0.31-0.57, estimating a carrier frequency of 5% in the Iranian population. CONCLUSIONS: Our data show that the SMA carrier frequency in Iran is higher than in the European population and that further programs of population carrier detection and prenatal testing should be implemented.


Asunto(s)
Eliminación de Gen , Tamización de Portadores Genéticos/métodos , Heterocigoto , Atrofia Muscular Espinal/genética , Mutación/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Adulto , Niño , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Pruebas Genéticas/normas , Genotipo , Humanos , Irán/etnología , Masculino , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/etnología , Programas Nacionales de Salud , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
6.
Haemophilia ; 14(5): 1094-8, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18665854

RESUMEN

Haemophillia A (HA) is an X-linked bleeding disorder caused by mutations in the F8 gene. While the disease affects 1 in 5000 males, phenotypic expression of haemophilia A is rare in females, similar to other X-linked recessive disorders. We describe a 5-year-old female with severe haemophilia A. We determined the underlying molecular defect in the F8 genes of the proband and her closest family members by direct DNA sequencing, marker analysis and quantitative real-time polymerase chain reaction. The patient showed two different mutations in the F8 gene: the paternal copy of the F8 gene had a de novo p.Phe652/653 deletion in exon 13 while the maternally inherited gene showed a large deletion encompassing exons 1 to 22. The structural analysis of residues Phe652/Phe653 based on a three-dimensional model of activated factor VIII provides evidence of the impact of the mutant factor VIII protein in the clinical manifestations of the patient. This unusual finding highlights the need to perform a thorough molecular analysis including sequencing, marker and quantitative analyses to identify compound heterozygous females with HA.


Asunto(s)
Factor VIII/genética , Eliminación de Gen , Hemofilia A/genética , Secuencia de Bases , Preescolar , Codón/genética , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Modelos Moleculares , Linaje , Reacción en Cadena de la Polimerasa/métodos
7.
Haemophilia ; 14(3): 489-93, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18384354

RESUMEN

We describe the usefulness of two dinucleotide repeats located in intron 9 and in intron 25 of the factor VIII gene for carrier diagnosis of haemophilia A. We analyzed 100 unrelated Spanish women and 34 women from haemophilia A (HA) families in whom known intragenic markers were unhelpful in determining their carrier status. The heterozygosity rate of intron 9 and intron 25 markers in the 100 control women was lower (0.28 and 0.38, respectively) than the values obtained with common markers routinely used in our laboratory. However, the application of intron 9 and intron 25 markers was effective in identifying the at-risk X chromosome in 11 of 34 (32%) of the uninformative women from HA families. The combined use of these repeats with current markers may facilitate the identification of the X chromosome in HA families for application in carrier, prenatal and pre-implantation diagnoses.


Asunto(s)
Repeticiones de Dinucleótido/genética , Factor VIII/genética , Hemofilia A/genética , Intrones , Secuencia de Bases , Cromosomas Humanos X/genética , Femenino , Frecuencia de los Genes/genética , Tamización de Portadores Genéticos/métodos , Hemofilia A/diagnóstico , Humanos , Reacción en Cadena de la Polimerasa , Embarazo , Diagnóstico Prenatal/métodos , España
8.
Genet Couns ; 18(1): 99-104, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17515305

RESUMEN

We present a 16 years old female with a chromosomal mixoploidy and multiple phenotypic anomalies. Peripheral blood G-band karyotype was 47,XXX and her skin fibroblast karyotype revealed a mosaic with a 47,XXX cell line in 88% of metaphases and a 94,XXXXXX cell line in 12% of metaphases, consistent with a hypertetraploidy. The most prominent clinical signs were: short stature, left upper limb asymmetry, senile-like appearance, generalized hypertrichosis, and small hands and feet. Radiological examination showed bone dysplasia. The result of molecular studies demonstrated that the patient inherited the two X chromosomes from the mother and one from the father, indicating that her 47,XXX trisomy resulted from an oogenesis error in the first meiotic division. The 94,XXXXXX cell line was likely the result of a cytokinesis error. To our knowledge, this is the first documented patient with a trisomy and a hypertetraploidy.


Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos X , Poliploidía , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales/genética , Trisomía/genética , Adolescente , Femenino , Humanos , Cariotipificación , Mosaicismo
9.
J Neurol ; 253(1): 21-5, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15981080

RESUMEN

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects motor neurons. It is caused by mutations in the survival motor neuron gene 1 (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present in all the patients, is unable to prevent the disease. An SMN2 dosage method was applied to 45 patients with the three SMA types (I-III) and to four pairs of siblings with chronic SMA (II-III) and different phenotypes. Our results confirm that the SMN2 copy number plays a key role in predicting acute or chronic SMA. However, siblings with different SMA phenotypes show an identical SMN2 copy number and identical markers, indicating that the genetic background around the SMA locus is insufficient to account for the intrafamilial variability. In our results, age of onset appears to be the most important predictor of disease severity in affected members of the same family. Given that SMN2 is regarded as a target for potential pharmacological therapies in SMA, the identification of genetic factors other than the SMN genes is necessary to better understand the pathogenesis of the disease in order to implement additional therapeutic approaches.


Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Salud de la Familia , Dosificación de Gen , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN/genética , Adulto , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia Muscular Espinal/clasificación , Proteínas del Tejido Nervioso/metabolismo , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas del Complejo SMN , Proteína 1 para la Supervivencia de la Neurona Motora , Proteína 2 para la Supervivencia de la Neurona Motora
10.
Neurology ; 48(5): 1443-5, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9153488

RESUMEN

The characterization of deletions in the SMN gene provides a helpful tool to confirm the diagnosis of spinal muscular atrophy (SMA). However, there may be homozygous deletions of the SMN gene in some unaffected siblings of SMA type II and III patients. We present two SMA families with affected siblings demonstrating a homozygous deletion of the SMN gene with extremely different phenotypes. We propose a preclinical category of an SMA patient with homozygous deletion of the SMN gene: those with minimal expression of the disease including cramps and EMG abnormalities that may develop the complete SMA phenotype in the future.


Asunto(s)
Eliminación de Gen , Homocigoto , Calambre Muscular/etiología , Músculos/fisiopatología , Atrofia Muscular Espinal/complicaciones , Atrofia Muscular Espinal/genética , Adolescente , Adulto , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia Muscular Espinal/fisiopatología , Linaje , Polimorfismo Conformacional Retorcido-Simple
11.
Neurology ; 59(9): 1456-60, 2002 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-12427907

RESUMEN

The presence of the SMN2 deletion in 124 patients with ALS was investigated. Eleven patients had the homozygous deletion of SMN2 (8.8%) in comparison with 20 of 200 (10%) of the healthy control population. No significant differences in sex, age at onset, initial symptoms, form of inheritance, decline in ventilatory function, or survival time were found between patients with and without the deletion. The hypothesis that SMN2 is a prognostic factor in sporadic or familial ALS was not confirmed in this study.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/mortalidad , Eliminación de Gen , Proteínas del Tejido Nervioso/genética , Mecánica Respiratoria , Adulto , Anciano , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Progresión de la Enfermedad , Femenino , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Análisis de Supervivencia , Proteína 2 para la Supervivencia de la Neurona Motora , Capacidad Vital
12.
Thromb Haemost ; 73(1): 6-9, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7740498

RESUMEN

Inversion involving intron 22 is the commonest type of mutation causing severe hemophilia A (HA). We investigated 15 families with isolated cases and 5 families with two or three brothers as the only affected members with hemophilia A, in order to determine the carrier status of the mothers, the origin of the mutation and the presence of germinal mosaicism. Our results show that all mothers tested were carriers of the inversion. In addition, three families whose unique hemophilic member was not available for analysis, were screened for the inversion. In one of these last families, the mother was diagnosed as a carrier and her sister and her niece as non-carriers. DNA haplotype analysis in 8 families with grandparents available for study demonstrated that the inversion originated almost exclusively in male germ cells. These findings have important relevance for genetic counselling in families with an isolated case or to exclude germinal mosaicism. Inversion analysis should constitute the first step in molecular diagnosis of severe hemophilia A.


Asunto(s)
Inversión Cromosómica , Factor VIII/genética , Hemofilia A/genética , Intrones , Femenino , Tamización de Portadores Genéticos , Asesoramiento Genético , Haplotipos/genética , Humanos , Masculino , Mosaicismo , Linaje , Cromosoma X
14.
J Pediatr ; 122(6): 985-8, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8501582

RESUMEN

After the discovery of the gene, the next major landmark will be the elucidation of the basic defect of the disorder, which should lead to rational treatments. The accumulating knowledge of mutations and phenotypes allows more accurate testing and screening in selected populations. Considerable information is now available both on the pattern of gene and protein expression in the tissues involved in the disease and on the complex regulation and function of CFTR. In addition, an animal model with which to test therapeutic strategies has become available. Finally, two potential ways to cure the disease have emerged: that which exploits our knowledge of the normal and the mutant protein and their function, and that based on gene therapy. The latter approach is probably beginning to be tested on small groups of patients, and proof of its effectiveness is eagerly awaited.


Asunto(s)
Fibrosis Quística , Animales , Fibrosis Quística/fisiopatología , Fibrosis Quística/terapia , Humanos
15.
Ann Intern Med ; 123(4): 305-8, 1995 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-7541969

RESUMEN

The cloning of the defective gene in cystic fibrosis (CFTR) is the most important step to date toward understanding the pathogenesis of the disease and developing novel therapeutic strategies. Although many studies have provided insights into the molecular defects and knowledge of the expression and role of the gene, the basic defect and its pathogenesis are still unclear. We hypothesize that organ damage in cystic fibrosis is the result of a combination of at least three main factors: the genotype (the type of mutation that alters the function of the cystic fibrosis transmembrane regulator [CFTR]), the rate of CFTR-mediated chloride secretion in the epithelium of each organ (inferred from the level of expression of the gene), and the anatomical and physiologic characteristics of the affected organs (the size and contents of the ducts). Confirmation of this hypothesis should allow a better understanding of the pathogenesis of the disease and help prevent organ damage.


Asunto(s)
Fibrosis Quística/genética , Proteínas de la Membrana/genética , Canales de Cloruro/metabolismo , Fibrosis Quística/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Regulación de la Expresión Génica , Genotipo , Humanos , Proteínas de la Membrana/metabolismo , Mutación
16.
Haemophilia ; 8(3): 250-4, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12010419

RESUMEN

Mutations in factor VIII and IX genes have a determinant effect on the severity of haemophilia. Modulation of clinical manifestations depends on other genetic factors, including modifier genes. In the context of haemophilia, such genes could be the ones involved in thrombophilia. Factor V Leiden and prothrombin 20210A were studied as possible phenotypic modifiers. Inhibitor development after therapeutic factor replacement depends on the type of mutation and on the genetic factors related to the immune response of each patient. The study of all these variants in haemophiliacs constitutes an important step in prevention, prognosis and therapeutic alternatives of the disease.


Asunto(s)
Hemofilia A/genética , Factor VIII/genética , Factor VIII/inmunología , Predisposición Genética a la Enfermedad/genética , Genoma Humano , Hemofilia A/inmunología , Humanos , Isoanticuerpos/genética , Isoanticuerpos/inmunología , Fenotipo
17.
Haemophilia ; 9(5): 584-7, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14511298

RESUMEN

Inversion of intron 22, the most frequent mutation event in haemophilia A (HA), was tested in our HA families to diagnose the females at risk of being carriers, to trace the origin of the mutation and to investigate the presence of germinal or somatic mosaicism. A total of 166 females belonging to 54 families with inversion, were analysed. All but one of the mothers tested were carriers and the inversion originated almost exclusively in male germ cells. Somatic or germline mosaicisms were excluded in 53 of these women and in 20 grandfathers, suggesting that such mosaicisms may be a rare event in families with inversion of intron 22.


Asunto(s)
Inversión Cromosómica , Hemofilia A/genética , Intrones/genética , Mosaicismo , Femenino , Tamización de Portadores Genéticos/métodos , Humanos , Masculino , Linaje
18.
Am J Pathol ; 153(2): 355-61, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9708795

RESUMEN

Spinal muscular atrophy is an autosomal recessive disorder characterized by the progressive loss or degeneration of the motor neurons. To investigate the expression of survival motor neuron (SMN), the spinal muscular atrophy-determining gene, and its relationship with the pathogenesis of the disease, we analyzed by means of in situ hybridization the location of SMN mRNA in fetal, newborn, infant, and adult human central nervous system tissues. The large motor neurons of the spinal cord are the main cells that express SMN together with the neurons of the medulla oblongata, the pyramidal cells of the cortex, and the Purkinje cells of the cerebellum. Some sensory neurons from the posterior horn and dorsal root ganglia express SMN to a lesser degree. Furthermore, strong SMN expression is detected in the ependymal cells of the central canal. The expression is present in the spinal cord at 8 weeks of fetal life throughout postnatal and adult life. The sharp expression of SMN in the motor neurons of the human spinal cord, the target cells in spinal muscular atrophy, suggests that this gene is implicated in neuronal development and in the pathogenesis of the disease. The location of the SMN gene expression in other neuronal structures not clearly or directly associated with clinical manifestations or pathological findings of spinal muscular atrophy may indicate a varying sensitivity to the absence or dysfunction of the SMN gene in motor neurons.


Asunto(s)
Sistema Nervioso Central/metabolismo , Regulación del Desarrollo de la Expresión Génica , Neuronas Motoras/metabolismo , Proteínas del Tejido Nervioso/genética , Adulto , Sistema Nervioso Central/embriología , Cerebelo/embriología , Cerebelo/metabolismo , Corteza Cerebral/embriología , Corteza Cerebral/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Humanos , Hibridación in Situ , Lactante , Recién Nacido , Bulbo Raquídeo/embriología , Bulbo Raquídeo/metabolismo , Persona de Mediana Edad , ARN/análisis , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Médula Espinal/embriología , Médula Espinal/metabolismo
19.
Hum Mol Genet ; 2(3): 219-24, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7684640

RESUMEN

An improved understanding of the expression of the cystic fibrosis gene (CFTR) will assist our approach to preventing the organ damage caused by cystic fibrosis (CF). We have studied the expression of CFTR in human fetal tissues at different gestational ages using in situ hybridization to detect CFTR mRNA. CFTR was principally expressed in less differentiated cells of endodermal origin. The highest levels were seen in specific areas of the developing pancreas, liver, gall bladder and intestine, with lower but significant levels in lung and trachea. Expression was also seen in reproductive tissues, such as epididymis and third trimester uterus and fallopian tubes, and in addition, sweat and salivary glands. No detection of CFTR mRNA was found in many other relevant tissues. The detection of CFTR transcript in these organs is consistent with the clinical manifestations of CF and the function of CFTR as a chloride channel early in development. The localization and levels of expression described have implications regarding the pathogenesis of organ damage and the potential gains that can be achieved by early therapy in the disease.


Asunto(s)
Fibrosis Quística/genética , Feto/metabolismo , Proteínas de la Membrana/genética , ARN Mensajero/genética , Fibrosis Quística/embriología , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Sistema Digestivo/metabolismo , Femenino , Regulación de la Expresión Génica , Genitales/metabolismo , Humanos , Masculino , Embarazo , ARN Mensajero/metabolismo , Sistema Respiratorio/metabolismo , Distribución Tisular
20.
Am J Pathol ; 144(5): 906-14, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-7513949

RESUMEN

Cystic fibrosis (CF) is characterized by a wide spectrum of clinical manifestations, including reproductive problems. Practically all males affected by the disease are infertile due to azoospermia associated with pathology of the male ducts, whereas females with CF have reduced fertility. To study the mechanism of reproductive pathology in CF patients, we analyzed the levels and localization of expression of the cystic fibrosis transmembrane regulator (CFTR) gene in relevant postnatal tissues. Significant expression was detected in the epithelium of the epididymis and vas deferens. Minimal expression, not associated with specific cell types, was seen in the mature testis. In female genitalia, variable levels of expression were seen in the cervical epithelium and fallopian tube. The endometrial epithelium and glands expressed CFTR at high levels only after puberty. No expression was seen in ovaries. Deficient secretory function of CFTR in males but not in females may lead to organ damage probably as a consequence of excessive concentration of viscid luminal contents.


Asunto(s)
Cuello del Útero/química , Fibrosis Quística , Endometrio/química , Trompas Uterinas/química , Proteínas de la Membrana/análisis , Testículo/química , Conducto Deferente/química , Adulto , Fibrosis Quística/complicaciones , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Epidídimo/química , Femenino , Humanos , Hibridación in Situ , Lactante , Recién Nacido , Infertilidad/etiología , Masculino
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