Asunto(s)
Trastornos de la Motilidad Ciliar/diagnóstico , Trastornos de la Motilidad Ciliar/genética , Encefalocele/diagnóstico , Encefalocele/genética , Enfermedades Renales Poliquísticas/diagnóstico , Enfermedades Renales Poliquísticas/genética , Pruebas Genéticas , Humanos , Diagnóstico Prenatal , Retinitis PigmentosaRESUMEN
Baller-Gerold syndrome (BGS) is a rare autosomal recessive condition with radial aplasia/hypoplasia and craniosynostosis (OMIM 218600). Of >20 cases reported so far, a few appear atypical and have been reassigned to other nosologic entities, including Fanconi anaemia, Roberts SC phocomelia, and Pfeiffer syndromes after demonstration of corresponding cytogenetic or molecular abnormalities. Clinical overlap between BGS, Rothmund-Thomson syndrome (RTS), and RAPADILINO syndrome is noticeable. Because patients with RAPADILINO syndrome and a subset of patients with RTS have RECQL4 mutations, we reassessed two previously reported BGS families and found causal mutations in RECQL4 in both. In the first family, four affected offspring had craniosynostosis and radial defect and one of them developed poikiloderma. In this family, compound heterozygosity for a R1021W missense mutation and a g.2886delT frameshift mutation of exon 9 was found. In the second family, the affected male had craniosynostosis, radial ray defect, poikiloderma, and short stature. He had a homozygous splice site mutation (IVS17-2A>C). In both families, the affected offspring had craniosynostosis, radial defects, and growth retardation, and two developed poikiloderma. Our results confirm that BGS in a subgroup of patients is due to RECQL4 mutations and could be integrated into a clinical spectrum that encompasses RTS and RAPADILINO syndrome.
Asunto(s)
Anomalías Múltiples/genética , Adenosina Trifosfatasas/genética , Craneosinostosis/genética , ADN Helicasas/genética , Mutación/genética , Radio (Anatomía)/patología , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , RecQ Helicasas , SíndromeRESUMEN
Developmental dyslexia is a distinct learning disability with unexpected difficulty in learning to read despite adequate intelligence, education, and environment, and normal senses. The genetic aetiology of dyslexia is heterogeneous and loci on chromosomes 2, 3, 6, 15, and 18 have been repeatedly linked to it. We have conducted a genome scan with 376 markers in 11 families with 38 dyslexic subjects ascertained in Finland. Linkage of dyslexia to the vicinity of DYX3 on 2p was confirmed with a non-parametric linkage (NPL) score of 2.55 and a lod score of 3.01 for a dominant model, and a novel locus on 7q32 close to the SPCH1 locus was suggested with an NPL score of 2.77. The SPCH1 locus has previously been linked with a severe speech and language disorder and autism, and a mutation in exon 14 of the FOXP2 gene on 7q32 has been identified in one large pedigree. Because the language disorder associated with the SPCH1 locus has some overlap with the language deficits observed in dyslexia, we sequenced the coding region of FOXP2 as a candidate gene for our observed linkage in six dyslexic subjects. No mutations were identified. We conclude that DYX3 appears to be important for dyslexia susceptibility in many Finnish families, and a suggested linkage of dyslexia to chromosome 7q32 will need verification in other data sets.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 7/genética , Dislexia/genética , Factores de Transcripción , Análisis Mutacional de ADN , Femenino , Finlandia , Factores de Transcripción Forkhead , Genoma Humano , Genotipo , Humanos , Escala de Lod , Masculino , Linaje , Proteínas Represoras/genéticaRESUMEN
Nephrin is a cell adhesion protein located at the slit diaphragm area of glomerular podocytes. Mutations in nephrin-coding gene (NPHS1) cause congenital nephrotic syndrome (NPHS1). We studied the developmental expression of nephrin, ZO-1 and P-cadherin in normal fetal kidneys and in NPHS1 kidneys. We used in situ hybridization and immunohistochemistry at light and electron microscopic levels. Nephrin and zonula occludens-1 (ZO-1) were first expressed in late S-shaped bodies. During capillary loop stage, nephrin and ZO-1 localized at the basal margin and in the cell-cell adhesion sites between developing podocytes, especially in junctions with ladder-like structures. In mature glomeruli, nephrin and ZO-1 concentrated at the slit diaphragm area. P-cadherin was first detected in ureteric buds, tubules, and vesicle stage glomeruli. Later, P-cadherin was seen at the basal margin of developing podocytes. Fetal NPHS1 kidneys with Fin-major/Fin-major genotype did not express nephrin, whereas the expression of ZO-1 and P-cadherin was comparable to that of control kidneys. Although early junctional complexes proved structurally normal, junctions with ladder-like structures and slit diaphragms were completely missing. The results indicate that nephrin is dispensable for early development of podocyte junctional complexes. However, nephrin appears to be essential for formation of junctions with ladder-like structures and slit diaphragms.
Asunto(s)
Feto/fisiología , Uniones Intercelulares/fisiología , Riñón/embriología , Proteínas/fisiología , Cadherinas/metabolismo , Desarrollo Embrionario y Fetal , Humanos , Glomérulos Renales/embriología , Proteínas de la Membrana/metabolismo , Microscopía Inmunoelectrónica , Mutación , Fosfoproteínas/metabolismo , Proteínas/genética , Valores de Referencia , Proteína de la Zonula Occludens-1RESUMEN
A second distinct family of anion transporters, in addition to the classical SLC4 (or AE) family, has recently been delineated. Members of the SLC26 family are structurally well conserved and can mediate the electroneutral exchange of Cl(-) for HCO(-)(3) across the plasma membrane of mammalian cells like members of the SLC4 family. Three human transporter proteins have been functionally characterized: SLC26A2 (DTDST), SLC26A3 (CLD or DRA), and SLC26A4 (PDS) can transport with different specificities the chloride, iodine, bicarbonate, oxalate, and hydroxyl anions, whereas SLC26A5 (prestin) was suggested to act as the motor protein of the cochlear outer hair cell. We report the expansion of the SLC26 family with five new members in chromosomes 3, 6, 8, 12, and 17 and mapping of SLC26A1 to 4p16.3. We have characterized one of them, SLC26A6, in more detail. It maps to chromosome 3p21.3, encodes a predicted 738-amino-acid transmembrane protein, and is most abundantly expressed in the kidney and pancreas. Pancreatic ductal cell lines Capan-1 and Capan-2 express SLC26A6, and immunohistochemistry localizes SLC26A6 protein to the apical surface of pancreatic ductal cells, suggesting it as a candidate for a luminal anion exchanger. The functional characterization of the novel members of this tissue-specific gene family may provide new insights into anion transport physiology in different parts of the body.
Asunto(s)
Aniones/metabolismo , Proteínas Portadoras/metabolismo , Familia de Multigenes , Páncreas/metabolismo , Empalme Alternativo , Secuencia de Aminoácidos , Proteínas de Transporte de Anión , Secuencia de Bases , Transporte Biológico , Proteínas Portadoras/genética , Humanos , Túbulos Renales , Modelos Moleculares , Datos de Secuencia Molecular , Polimorfismo Genético , Homología de Secuencia de Aminoácido , Distribución TisularRESUMEN
BACKGROUND: Congenital nephrotic syndrome (NPHS1) is a rare disease inherited as an autosomally recessive trait. The NPHS1 gene mutated in NPHS1 children has recently been identified. The gene codes for nephrin, a cell-surface protein of podocytes. Two mutations, named Fin-major and Fin-minor, have been found in over 90% of the Finnish patients. In this study, we correlated the NPHS1 gene mutations to the clinical features and renal findings in 46 Finnish NPHS1 children. METHODS: Clinical data were collected from patient files, and kidney histology and electron microscopy samples were re-evaluated. The expression of nephrin was studied using immunohistochemistry, Western blotting, and in situ hybridization. RESULTS: Nephrotic syndrome was detected in most patients within days after birth regardless of the genotype detected. No difference could be found in neonatal, renal, cardiac, or neurological features in patients with different mutations. Nephrin was not expressed in kidneys with Fin-major or Fin-minor mutations, while another slit diaphragm-associated protein, ZO-1, stained normally. In electron microscopy, podocyte fusion and podocyte filtration slits of various sizes were detected. The slit diaphragms, however, were missing. In contrast to this, a nephrotic infant with Fin-major/R743C genotype expressed nephrin in kidney had normal slit diaphragms and responded to therapy with an angiotensin-converting enzyme inhibitor and indomethacin. CONCLUSIONS: The most common NPHS1 gene mutations, Fin-major and Fin-minor, both lead to an absence of nephrin and podocyte slit diaphragms, as well as a clinically severe form of NPHS1, the Finnish type of congenital nephrotic syndrome.
Asunto(s)
Mutación Missense , Síndrome Nefrótico/genética , Proteínas/genética , Western Blotting , Finlandia , Expresión Génica , Genes Recesivos , Genotipo , Humanos , Hipoproteinemia/congénito , Hipoproteinemia/genética , Hibridación in Situ , Recién Nacido , Riñón/química , Riñón/ultraestructura , Proteínas de la Membrana/análisis , Proteínas de la Membrana/genética , Microscopía Electrónica , Síndrome Nefrótico/congénito , Fosfoproteínas/análisis , Fosfoproteínas/genética , Proteínas/análisis , Proteinuria/congénito , Proteinuria/genética , ARN Mensajero/análisis , Proteína de la Zonula Occludens-1RESUMEN
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.
Asunto(s)
Enfermedad de Alzheimer/genética , Quistes Óseos/genética , Células Asesinas Naturales , Proteínas de la Membrana/fisiología , Receptores Inmunológicos/fisiología , Proteínas Adaptadoras Transductoras de Señales , Adulto , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/etiología , Secuencia de Aminoácidos , Secuencia de Bases , Quistes Óseos/complicaciones , Quistes Óseos/epidemiología , Quistes Óseos/etiología , ADN Complementario , Finlandia/epidemiología , Humanos , Japón/epidemiología , Proteínas de la Membrana/genética , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutagénesis , Receptores Inmunológicos/genética , Eliminación de SecuenciaRESUMEN
We describe here the size and location of nephrin, the first protein to be identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin antibodies generated against the two terminal extracellular Ig domains of recombinant human nephrin recognized a 180-kDa protein in lysates of human glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In immunofluorescence, antibodies to this transmembrane protein revealed reactivity in the glomerular basement membrane region, whereas the podocyte cell bodies remained negative. In immunogold-stained thin sections, nephrin label was found at the slit between podocyte foot processes. The congenital nephrotic syndrome of the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is characterized by massive proteinuria already in utero and lack of slit diaphragm and foot processes. These features, together with the now demonstrated localization of nephrin to the slit diaphragm area, suggests an essential role for this protein in the normal glomerular filtration barrier. A zipper-like model for nephrin assembly in the slit diaphragm is discussed, based on the present and previous data.
Asunto(s)
Células Epiteliales/fisiología , Células Epiteliales/ultraestructura , Glomérulos Renales/fisiología , Glomérulos Renales/ultraestructura , Proteínas/análisis , Proteínas/genética , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Clonación Molecular , Finlandia , Tasa de Filtración Glomerular , Humanos , Proteínas de la Membrana , Microscopía Inmunoelectrónica , Datos de Secuencia Molecular , Mutación , Síndrome Nefrótico/genética , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes/análisisAsunto(s)
Enfermedades Fetales/diagnóstico , Síndrome Nefrótico/diagnóstico , Diagnóstico Prenatal , alfa-Fetoproteínas/metabolismo , Amniocentesis , Femenino , Enfermedades Fetales/sangre , Tamización de Portadores Genéticos , Edad Gestacional , Humanos , Síndrome Nefrótico/sangre , Síndrome Nefrótico/congénito , EmbarazoRESUMEN
Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal recessive disorder that is caused by mutations in the recently discovered nephrin gene, NPHS1 (AF035835). The disease, which belongs to the Finnish disease heritage, exists predominantly in Finland, but many cases have been observed elsewhere in Europe and North America. The nephrin gene consists of 29 exons spanning 26 kb in the chromosomal region 19q13.1. In the present study, the genomic structure of the nephrin gene was analyzed, and 35 NPHS1 patients were screened for the presence of mutations in the gene. A total of 32 novel mutations, including deletions; insertions; nonsense, missense, and splicing mutations; and two common polymorphisms were found. Only two Swedish and four Finnish patients had the typical Finnish mutations: a 2-bp deletion in exon 2 (Finmajor) or a nonsense mutation in exon 26 (Finminor). In seven cases, no mutations were found in the coding region of the NPHS1 gene or in the immediate 5'-flanking region. These patients may have mutations elsewhere in the promoter, in intron areas, or in a gene encoding another protein that interacts with nephrin.
Asunto(s)
Mutación Missense , Síndrome Nefrótico/congénito , Síndrome Nefrótico/genética , Proteínas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 19 , Cósmidos , ADN/química , Análisis Mutacional de ADN , Finlandia/epidemiología , Humanos , Incidencia , Recién Nacido , Proteínas de la Membrana , Datos de Secuencia Molecular , Síndrome Nefrótico/epidemiologíaRESUMEN
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770) is a rare hereditary cause of presenile dementia with autosomal recessive inheritance. Its unique feature is the cystic bone lesions that accompany the dementia. About 160 cases have been reported to date, mostly in Finland and Japan. The etiology and pathogenesis of PLOSL are unknown. We recently assigned the locus for PLOSL in the Finnish population to chromosome 19q13.1 (P. Pekkarinen et al., 1998, Am. J. Hum. Genet. 62, 362-272). In the present study, we restrict the critical region for PLOSL to 153 kb by linkage-disequilibrium mapping. First, three new microsatellite markers were revealed in the PLOSL critical region. These and three other markers spanning the critical region were analyzed in Finnish PLOSL families. Strong linkage disequilibrium (multipoint P value < 10(-47)) was detected between the markers and PLOSL, and for two markers, D19S1176 and D19S610, all the PLOSL chromosomes shared identical 171- and 218-bp alleles, respectively. Haplotype analysis revealed five different haplotypes in the Finnish PLOSL chromosomes. But all of them shared the region between markers D19S1175 and D19S608 that could be traced to one ancestor haplotype by single recombination events, thus defining the critical region as 153 kb. Multipoint association analysis also assigned the most likely location of the PLOSL locus within this interval to the immediate vicinity of marker D19S610. A promising positional candidate for PLOSL, an amyloid precursor-like protein, was studied by sequencing, but no mutations were detected. These results lay the basis for the cloning of this novel dementia gene and for diagnostics in the Finnish population using haplotype analysis.
Asunto(s)
Mapeo Cromosómico , Demencia/genética , Desequilibrio de Ligamiento/genética , Proteínas/genética , Receptores Inmunológicos , Proteínas Adaptadoras Transductoras de Señales , Alelos , Cromosomas Humanos Par 19/genética , Demencia/epidemiología , Demografía , Femenino , Finlandia , Ligamiento Genético/genética , Haplotipos/genética , Humanos , Escala de Lod , Masculino , Proteínas de la Membrana , Repeticiones de Microsatélite/genética , Datos de Secuencia Molecular , Linaje , Mapeo Físico de CromosomaRESUMEN
Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of NPHS1 was sequenced, revealing the presence of at least 11 genes, the structures of 5 of which were determined. Four different mutations segregating with the disease were found in one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a 1241-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli. The results demonstrate a crucial role for this protein in the development or function of the kidney filtration barrier.
Asunto(s)
Eliminación de Gen , Glomérulos Renales/química , Síndrome Nefrótico/congénito , Síndrome Nefrótico/genética , Proteínas/genética , Secuencia de Aminoácidos , Clonación Molecular , Cósmidos , Análisis Mutacional de ADN , ADN Complementario/aislamiento & purificación , Exones/genética , Salud de la Familia , Expresión Génica , Haplotipos , Humanos , Inmunoglobulinas/genética , Glomérulos Renales/fisiopatología , Proteínas de la Membrana , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Proteínas/química , ARN Mensajero/genéticaRESUMEN
A total of 17 histologically confirmed olfactory neuroblastomas treated at Helsinki University Central Hospital between 1962 and 1996 were reviewed retrospectively. The tumors displayed a variety of imaging characteristics and aggressiveness. Imaging evolved from plain X-rays at the beginning of the study period to CT and MRI during the latter part of the study. CT provided the best information about the tumor and its local invasion especially into surrounding bony structures. MRI allowed an estimate of tumor spread into surrounding soft-tissue areas, such as the anterior cranial fossa and the retromaxillary space. However, signal intensity characteristics were not specific for olfactory neuroblastomas. Bone scintigraphy and MIBG scan allowed us to detect distant metastases. Olfactory neuroblastoma is an aggressive malignancy and the prognosis is poor in most cases, as shown by the short survival rates (average 45.3 months) in our study group. The tumor can be detected, delineated and its characteristics suspected by modern radiology. Definite diagnosis is based on histopathology. This study proposes general imaging strategies for detecting this disease.
Asunto(s)
Diagnóstico por Imagen , Estesioneuroblastoma Olfatorio/diagnóstico , Neoplasias Nasales/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Preescolar , Estesioneuroblastoma Olfatorio/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cavidad Nasal/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Nasales/patología , Sensibilidad y EspecificidadRESUMEN
PLO-SL (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy) is a recessively inherited disorder characterized by systemic bone cysts and progressive presenile frontal-lobe dementia, resulting in death at <50 years of age. Since the 1960s, approximately 160 cases have been reported, mainly in Japan and Finland. The pathogenesis of the disease is unknown. In this article, we report the assignment of the locus for PLO-SL, by random genome screening using a modification of the haplotype-sharing method, in patients from a genetically isolated population. By screening five patient samples from 2 Finnish families, followed by linkage analysis of 12 Finnish families, 3 Swedish families, and 1 Norwegian family, we were able to assign the PLO-SL locus to a 9-cM interval between markers D19S191 and D19S420 on chromosome 19q13. The critical region was further restricted, to approximately 1.8 Mb, by linkage-disequilibrium analysis of the Finnish families. According to the haplotype analysis, one Swedish and one Norwegian PLO-SL family are not linked to the chromosome 19 locus, suggesting that PLO-SL is a heterogeneous disease. In this chromosomal region, one potential candidate gene for PLO-SL, the gene encoding amyloid precursor-like protein 1, was analyzed, but no mutations were detected in the coding region.
Asunto(s)
Precursor de Proteína beta-Amiloide/genética , Quistes Óseos/genética , Cromosomas Humanos Par 19 , Demencia/genética , Proteínas del Tejido Nervioso/genética , Adolescente , Adulto , Quistes Óseos/epidemiología , Quistes Óseos/mortalidad , Mapeo Cromosómico , Demencia/epidemiología , Demencia/mortalidad , Familia , Femenino , Finlandia/epidemiología , Lóbulo Frontal , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo Conformacional Retorcido-Simple , PrevalenciaRESUMEN
Amyloid-precursor-like protein 1 (APLP1) is a membrane-associated glycoprotein, whose gene is homologous to the APP gene, which has been shown to be involved in the pathogenesis of Alzheimer's disease. APLP1 is predominantly expressed in brain, particularly in the cerebral cortex postsynaptic density. The genomic organization of mouse APLP1 has been determined, and the human gene has been mapped to chromosomal region 19q13.1. In the present study, the entire sequence of human APLP1 has been determined from a cosmid clone, and the genomic structure has been determined. The gene is 11.8 kb long and contains 17 exons. We have previously mapped the gene for congenital nephrotic syndrome (CNF) to the APLP1 region, to the vicinity of marker D19S610 located between markers D19S191 and DS19608. APLP1 is the only known gene in the vicinity of the marker D19S610. Because of its location and the proposed interference of amyloid with basement membrane assembly, APLP1 has been considered a candidate gene for CNF. All exon regions of the gene were amplified by the polymerase chain reaction and sequenced from DNA of CNF patients. No differences were observed between CNF patients and controls, suggesting that mutations in APLP1 are not involved in the etiology of CNF.
Asunto(s)
Precursor de Proteína beta-Amiloide/análogos & derivados , Cromosomas Humanos Par 19/genética , Adulto , Precursor de Proteína beta-Amiloide/biosíntesis , Precursor de Proteína beta-Amiloide/genética , Clonación Molecular , ADN Complementario/análisis , ADN Complementario/aislamiento & purificación , Exones , Expresión Génica , Humanos , Datos de Secuencia Molecular , Síndrome Nefrótico/congénito , Síndrome Nefrótico/genética , Especificidad de Órganos/genética , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Haplotype analysis and alpha-fetoprotein quantitation comprise a prenatal diagnosis of congenital nephrosis. Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease characterized by massive proteinuria and nephrotic syndrome from birth. Prenatal diagnosis of CNF has previously been based on the quantitation of alpha-fetoprotein (AFP) in the amniotic fluid and maternal serum, but an increased AFP is not specific for the disease. We have recently localized the CNF gene to the chromosome 19q13.1 region and observed a strong linkage disequilibrium to the genetic markers D19S610, D19S608, D19S224 and D19S220 in this chromosomal area. Four main CNF-haplotypes have been observed in Finnish kindreds. In the present study, linkage and haplotype analyses have been applied to prenatal diagnosis of six families with a history of CNF. The results diminish the risk of false positive diagnosis and abortions of healthy fetuses in families at risk.
Asunto(s)
Análisis Mutacional de ADN/métodos , Síndrome Nefrótico/congénito , Síndrome Nefrótico/diagnóstico , Diagnóstico Prenatal/métodos , Líquido Amniótico/química , Factor Natriurético Atrial/análisis , Factor Natriurético Atrial/sangre , Cromosomas Humanos Par 19/genética , Estudios de Evaluación como Asunto , Femenino , Finlandia , Genes Recesivos , Marcadores Genéticos , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Síndrome Nefrótico/genética , Linaje , Embarazo , Factores de RiesgoRESUMEN
Congenital nephrotic syndrome of the Finnish type (CNF) has an estimated incidence of 1 in 8000 newborns in the genetically isolated population of Finland. Although the disease is most common in Finland, it occurs throughout the world in families without known Finnish origin. In the past, these authors recently localized the CNF gene to the chromosome 19q13.1 region and observed strong linkage disequilibrium to the genetic markers D19S610, D19S608, D19S224, and D19S220 in Finnish families. In these Finnish families, four main CNF haplotype categories have been observed. In the study presented here, haplotype analysis was applied to several non-Finnish CNF families to determine whether the same genetic locus is involved in these families. The results of the haplotype analysis suggest linkage to the 19q13.1 chromosomal region. It was also observed that, in most cases, alleles typically found on CNF chromosomes of Finnish families are also found on CNF chromosomes of non-Finnish families from North America and Europe. In these families, the strongest association was found with marker D19S608. These findings suggest that Finnish and many non-Finnish CNF cases share the same disease locus.
Asunto(s)
Haplotipos , Síndrome Nefrótico/congénito , Síndrome Nefrótico/genética , Alelos , Mapeo Cromosómico , Cromosomas Humanos Par 19/genética , Europa (Continente) , Femenino , Finlandia , Marcadores Genéticos , Humanos , Desequilibrio de Ligamiento , Masculino , América del Norte , LinajeRESUMEN
Ultrashort-lived tracer 191mIr (T1/2 = 4.92 s) can be obtained with a high yield from an 191Os/191mIr generator with a low 191Os breakthrough. It was eluated directly into the tail veins of Wistar rats. These animals were imaged dynamically (five frames/s) up to 40 s. The measurement was repeated five times on each animal. The whole-body retention and biodistribution of 191Os was studied by sacrificing the rats at one and four days, respectively, after injection. The activity retained was highest in the kidneys and the spleen, followed by the muscles and the liver. These values indicate that the breakthrough is by no means dangerous and that investigations can be repeated immediately with a radiation exposure of no significance. Furthermore, all investigations in the same animal were reproducible, suggesting that 191mIr might be a good tracer for nuclear angiograms.
Asunto(s)
Radioisótopos de Iridio/farmacocinética , Animales , Semivida , Riñón/metabolismo , Hígado/metabolismo , Músculo Esquelético/metabolismo , Osmio , Radioisótopos , Ratas , Ratas Wistar , Bazo/metabolismo , Factores de Tiempo , Distribución TisularRESUMEN
Iridium-191m (191mIr, t1/2 = 4.96 sec), an ultra-short lived tracer, has turned out to be suitable for gamma imaging. It can be obtained in high yields from an 191Os/191mIr-generator with a low 191Os breakthrough. In this study the blood flow in the carotid and kidney arteries was studied in rabbits by radionuclide arteriograms. In addition, the whole body retention and biodistribution of 191Os was studied in rats. 191mIr was obtained from an activated carbon system, in a modification of the procedure described in the literature. The kidney regions (study I) of rabbits were imaged dynamically (5 frames/second) for up to 40 seconds, and the investigations were repeated 4-7 times in the same animal. Similarly, the carotid arteries were studied (study II) and from the curves flow parameters were calculated. In order to study the 191Os breakthrough two groups of rats (n = 5) were sacrificed one day and four days after injecting five diagnostic doses into the tail vein (study III). In study III the Os-retention was highest in the kidneys and spleen, followed by the muscles and liver: 0.11-0.12% ID/g tissues were obtained at 1 day and 0.10-0.13% ID/g at 4 days, respectively. These values indicate that the breakthrough values are by no means toxic and that investigations can be repeated immediately with a negligible radiation exposure. The investigations performed with the same animals (I-II) could be easily repeated and were reproducible. All of this indicates that 191mIr is suitable for radionuclide angiography and the generator system is simple and safe to use (191Os is beta-emitter).(ABSTRACT TRUNCATED AT 250 WORDS)