RESUMEN
COVID-19 led to the reconfiguration of U.K. orthopaedic trauma services because surgical capacity was threatened in acute centers. We report the 30-day mortality of proximal femoral fractures in older adults treated at an elective orthopaedic center. METHODS: Patients >60 years old who presented with a proximal femoral fracture to any of 4 sites in the regional trauma network were transferred to our elective center for emergency surgery. Care was modeled according to the National Institute for Health and Care Excellence guidelines, and efforts were made to treat all patients within 36 hours. Data were collected prospectively, and mortality outcomes were recorded. RESULTS: Of the 192 patients who presented to the elective orthopaedic center, 167 were treated there. The median age of the latter patients was 88 years (interquartile range, 83 to 79 years). The median Charlson Comorbidity Index was 4 (interquartile range, 4 to 6). The median time from emergency department admission to surgical treatment was 24.5 hours (interquartile range, 18.8 to 34.7 hours). The 30-day rate of mortality was 10.2%. A total of 29 (17.4%) tested positive for COVID-19 during their admission, of whom 10 died, for a case-fatality rate of 34.5%. There were no significant differences in age (p = 0.33) or Charlson Comorbidity Index (p = 0.13) between patients who tested positive and those who did not. There was no significant difference in age between those who tested positive and died and those who tested positive and did not die (p = 0.13), but there was a significant difference in Charlson Comorbidity Index between those subgroups (p = 0.03). CONCLUSIONS: During a pandemic, an elective orthopaedic center can be reconfigured to a surgical center for older patients with proximal femoral fractures with acceptable health-care quality outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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AIMS: We conducted a study to determine whether radiological parameters correlate with patient reported functional outcome, health-related quality of life and physical measures of function in patients with a fracture of the distal radius. PATIENTS AND METHODS: The post-operative palmar tilt and ulnar variance at six weeks and 12 months were correlated with the Patient Rated Wrist Evaluation, Disabilities of the Arm, Shoulder and Hand, and EuroQol scores, grip strength, pinch strength and range of movement at three, six and 12 months for 50 patients (mean age 57 years; 26 to 85) having surgical fixation, with either percutaneous pinning or reconstruction with a volar plate, for a fracture of the distal radius. RESULTS: Radiological parameters were found to correlate poorly with the patient reported outcomes (r = 0.00 to 0.47) and physical measures of function (r = 0.01 to 0.51) at all intervals. CONCLUSION: This study raises concerns about the use of radiological parameters to determine management, and to act as a surrogates for successful treatment, in patients with a fracture of the distal radius. Restoration of 'normal' radiographic parameters may not be necessary to achieve a satisfactory functional outcome for the patient. Cite this article: Bone Joint J 2017;99-B:376-82.
Asunto(s)
Fracturas del Radio/cirugía , Traumatismos de la Muñeca/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Evaluación de la Discapacidad , Femenino , Fijación Interna de Fracturas/métodos , Fuerza de la Mano , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Calidad de Vida , Radiografía , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/rehabilitación , Rango del Movimiento Articular , Recuperación de la Función , Traumatismos de la Muñeca/diagnóstico por imagen , Traumatismos de la Muñeca/rehabilitación , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/fisiopatología , Articulación de la Muñeca/cirugíaRESUMEN
We conducted an observational radiographic study to determine the inter- and intra-observer reliability of the AO classification of fractures of the distal radius. Plain posteroanterior and lateral radiographs of 456 patients with an acute fracture of the distal radius were classified by a consultant orthopaedic hand specialist and two specialist trainees, and the k coefficient for the inter- and intra-observer reliability of the type, group and subgroup classification was calculated. Only the type of fracture (A, B or C) was found to provide substantial intra-observer reliability (k type 0.65). The inclusion of 'group' and 'subgroup' into the classification reduced the inter-observer reliability to fair (kgroup 0.29, ksubgroup = 0.28) and the intra-observer reliability to moderate (kgroup 0.53, ksubgroup 0.49). Disagreement was found to arise between specific subgroups, which may be amenable to clarification.
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Fracturas del Radio/clasificación , Fracturas del Radio/diagnóstico por imagen , Humanos , Fracturas Intraarticulares/clasificación , Fracturas Intraarticulares/diagnóstico por imagen , Radiografía , Reproducibilidad de los Resultados , Fracturas del Cúbito/clasificación , Traumatismos de la Muñeca/clasificación , Traumatismos de la Muñeca/diagnóstico por imagenRESUMEN
The aim of this work was to identify NRL mutations in a panel of 200 autosomal dominant retinitis pigmentosa (adRP) families. All samples were subjected to heteroduplex analysis of the three exons of the NRL gene, and HphI restriction digest analysis of exon 2 (to identify the S50T mutation). Families found to have the S50T mutation, and six additional larger pedigrees (which had previously been excluded from the other nine adRP loci) underwent linkage analysis using polymorphic markers located in the region of 14q11. HphI restriction analysis followed by direct sequencing of the amplified NRL exon 2 product demonstrated the presence of the NRL S50T sequence change in three adRP families. Comparison of marker haplotypes in affected individuals from these families with those of affected members of the original 14q11 linked family revealed a common disease haplotype for markers within the adRP locus. Recombination events observed in these families define an adRP critical interval of 14.9 cM between D13S72 and D14S1041. Linkage analysis enabled all six of the larger adRP pedigrees to be excluded from the 14q11 locus. The NRL S50T mutation represents another example of a 'founder effect' in a dominantly inherited retinal dystrophy. Identification of such 'founder effects' may greatly simplify diagnostic genetic screening and lead to better prognostic counselling. The exclusion of several adRP families from all ten adRP loci indicates that at least one further adRP locus remains to be found.
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Proteínas de Unión al ADN/genética , Proteínas del Ojo/genética , Efecto Fundador , Genes Dominantes/genética , Mutación/genética , Retinitis Pigmentosa/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Mapeo Cromosómico , Análisis Mutacional de ADN , Cartilla de ADN/química , Femenino , Haplotipos , Análisis Heterodúplex , Humanos , Masculino , Repeticiones de Microsatélite , Linaje , Reacción en Cadena de la Polimerasa , Mapeo Restrictivo , Rodopsina/genéticaRESUMEN
Mutations in the RP2 gene located on Xp11.23 are associated with X-linked retinitis pigmentosa (XLRP), a severe form of progressive retinal degeneration which leads to complete loss of vision in affected males. To date, 14 different mutations in the RP2 gene have been reported to cause XLRP, the majority of which lead to a coding frameshift within the gene and predicted truncation of the protein product. We here report two novel frameshift mutations in RP2 identified in XLRP families by PCR-SSCP and direct sequencing, namely 723delT and 796-799del. Four single nucleotide polymorphisms (SNPs) within the coding region of RP2 are also described (105A>T, 597T>C, 844C>T, 1012G>T), the first polymorphisms to be reported within this gene of unknown function, two of which alter the amino acid sequence. The current study extends the XLRP mutation profile of RP2 and highlights non-pathogenic coding sequence variations which may facilitate both functional studies of the gene and analysis of intragenic allelic contribution to the phenotype.
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Proteínas del Ojo , Mutación del Sistema de Lectura/genética , Variación Genética/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas/genética , Empalme Alternativo/genética , Proteínas de Unión al GTP , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas de la Membrana , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
X-linked retinitis pigmentosa is a severe retinal degeneration characterized by night blindness and visual field constriction, leading to complete blindness within the third decade of life. Mutations in the RPGR gene (retinitis pigmentosa GTPase regulator), located on Xp21.1 in the RP3 region, have been associated with an RP phenotype. Further to our previous mutation screening of RPGR in families segregating with the RP3 locus, we have expanded this study to include other 8 RP3 pedigrees. Here we report the results of this expanded study and the identification of five mutations in RPGR, four of which are novel (IVS6+5 G>A, 950-951delAA, 963 T>C, EX8del) and one of which occurs in the donor splice site of intron 1 (IVS1+1 G>A). These findings bring the proportion of "RP3 genotypes" with a mutation in this gene to 27% (10/37). Hum Mutat 15:386, 2000.
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Proteínas Portadoras/genética , Proteínas del Ojo , Mutación/genética , Proteínas/genética , Retinitis Pigmentosa/genética , Bélgica , Mutación del Sistema de Lectura/genética , Marcadores Genéticos , Humanos , Nueva Zelanda , Retinitis Pigmentosa/diagnóstico , Eliminación de Secuencia/genética , Reino Unido , Estados UnidosRESUMEN
The guanylate cyclase activator proteins (GCAP1 and GCAP2) are calcium binding proteins which by activating Ret-GC1 play a key role in the recovery phase of phototransduction. Recently a mutation in the GUCA1A gene (coding for GCAP1) mapping to the 6p21.1 region was described as causing cone dystrophy in a British family. In addition mutations in Ret-GC1 have been shown to cause Leber congenital amaurosis and cone-rod dystrophy. To determine whether GCAP2 is involved in dominant retinal degenerative diseases, the GCAP2 gene was screened in 400 unrelated subjects with autosomal dominant central and peripheral retinal dystrophies. A number of changes involving the intronic as well as the coding sequence were observed. In exon 1 a T to C nucleotide change was observed leaving the tyrosine residue 57 unchanged. In exon 3 a 1 bp intronic insertion, a single nucleotide substitution G to A in the intron 3' of this exon, and a GAG to GAT change at codon 155 were observed. This latter change results in a conservative change of glutamic acid to aspartic acid. In exon 4 a 7 bp intronic insertion, a single nucleotide A to G substitution in the intron 5' of this exon, and a single base pair change C to G in the intron 3' of exon 4 were seen. None of these changes would be expected to affect correct splicing of this gene. All these changes were observed in controls. The results of this study do not show any evidence so far that GCAP2 is involved in the pathogenesis of autosomal dominant retinal degeneration in this group of patients. All the changes detected were found to be sequence variations or polymorphisms and not disease causing.
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Proteínas de Unión al Calcio/genética , Guanilato Ciclasa/genética , Degeneración Retiniana/genética , Exones , Proteínas Activadoras de la Guanilato-Ciclasa , Análisis Heterodúplex , HumanosRESUMEN
PURPOSE: To evaluate the intrafamilial phenotypic variation in Stargardt macular dystrophy-Fundus flavimaculatus (SMD-FFM). METHODS: Thirty-one siblings from 15 families with SMD-FFM were examined. Age of onset, visual acuity, and clinical features on fundus examination and fundus autofluorescence images, including presence or absence of central and peripheral atrophy and distribution of flecks, were recorded. In addition, electrophysiological studies were undertaken. RESULTS: Large differences between siblings in age of onset (median, 12 years; range, 5-23 years) were observed in six of the 15 families studied, whereas in 9 families differences in age of onset between siblings were small (median, 1 year; range, 0-3 years). Visual acuity varied two or more lines among siblings in nine families. In 10 families (67%) siblings were found to have different clinical appearance on fundus examination and fundus autofluorescence images, whereas in 5 families (33%), affected siblings had similar clinical features. Electrodiagnostic tests were performed on affected members of 12 families and disclosed similar qualitative findings among siblings. In nine families there was loss of central function only; in two, global loss of cone function; and in one, global loss of cone and rod function. CONCLUSIONS: In this series, although differences in age of onset, visual acuity, and fundus appearance were observed between siblings, electrophysiological studies demonstrated intrafamilial homogeneity in retinal function. The findings are difficult to reconcile with expression studies showing ABCR transcripts in rod photoreceptors but not in cones.
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Fondo de Ojo , Variación Genética , Degeneración Macular/genética , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Sensibilidad de Contraste , Electrooculografía , Electrorretinografía , Femenino , Humanos , Degeneración Macular/patología , Degeneración Macular/fisiopatología , Masculino , Linaje , Fenotipo , Estimulación Luminosa , Retina/fisiopatología , Agudeza VisualRESUMEN
The X-linked form of retinitis pigmentosa (XLRP) is a severe disease of the retina, characterised by night blindness and visual field constriction in a degenerative process, culminating with complete loss of sight within the third decade of life. Genetic mapping studies have identified two major loci for XLRP: RP3 (70%-75% of XLRP) and RP2 (20%-25% of XLRP). The RPGR (retinitis pigmentosa GTPase regulator) gene has been cloned within the RP3 genomic interval and it has been shown that 10%-20% of XLRP families have mutations in this gene. Here, we describe a single-strand conformational polymorphism-based mutation screening of RPGR in a pool of 29 XLRP families for which the disease segregates with the RP3 locus, in order to investigate the proportion of RP3 families with RPGR mutations and to relate the results to previous reports. Five different new mutations have been identified: two splice site mutations for exon 1 and three frameshift mutations in exons 7, 10 and 11. The percentage of RPGR mutations identified is 17% (5/29) in our genetically well-defined population. This figure is comparable to the percentage of RP2 gene mutations that we have detected in our entire XLRP patient pool (10%-15%). A correlation of RPGR mutations with phenotype in the families described in this study and the biochemical characterisation of reported mutations may provide insights into the function of the protein.
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Proteínas Portadoras/genética , Proteínas del Ojo , Mutación del Sistema de Lectura , Ligamiento Genético , Proteínas/genética , Retinitis Pigmentosa/genética , Cromosoma X , Secuencia de Bases , Exones , Femenino , Pruebas Genéticas , Genotipo , Haplotipos , Humanos , Intrones , Masculino , Modelos Genéticos , Datos de Secuencia Molecular , Linaje , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-SimpleAsunto(s)
Proteínas de Unión al ADN/genética , Proteínas del Ojo/genética , Mutación , Retinitis Pigmentosa/genética , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Línea Celular , Proteínas de Unión al ADN/metabolismo , Proteínas del Ojo/metabolismo , Femenino , Regulación de la Expresión Génica , Genes Dominantes , Ligamiento Genético , Marcadores Genéticos , Análisis Heterodúplex , Humanos , Leucina Zippers/genética , Masculino , Linaje , Regiones Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , TransfecciónRESUMEN
Doyne honeycomb retinal dystrophy (DHRD) is a late-onset autosomal dominant disorder that causes degeneration of the retina and can lead to blindness. We have previously assigned DHRD to a 5-cM region of chromosome 2p16 between marker loci D2S2739 and D2S378. Using sequence-tagged sites (STSs), expressed sequence tags (ESTs) and polymorphic markers within the DHRD region, we have identified 18 yeast artificial chromosomes (YACs) encompassing the DHRD locus, spanning approximately 3 Mb. The YAC contig was constructed by STS content mapping of these YACs and incorporates 13 STSs, including four genes and six polymorphic marker loci. We also report the genetic mapping of two families with a dominant drusen phenotype to the DHRD locus, and genetic refinement of the disease locus to a critical interval flanked by microsatellite marker loci D2S2352 and D2S2251, a distance of approximately 700 kb. These studies exclude a number of candidate genes and provide a resource for construction of a transcriptional map of the region, as a prerequisite to identification of the DHRD disease-causing gene and genes for other diseases mapping in the region, such as Malattia leventinese and Carney complex.
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Mapeo Contig/métodos , Degeneración Retiniana/genética , Cromosomas Artificiales de Levadura , Cromosomas Humanos Par 2/genética , Femenino , Marcadores Genéticos , Genotipo , Humanos , Escala de Lod , Masculino , Linaje , Recombinación Genética , Lugares Marcados de SecuenciaAsunto(s)
Proteínas del Ojo , Ligamiento Genético/genética , Mutación/genética , Proteínas/genética , Retinitis Pigmentosa/genética , Cromosoma X/genética , Secuencia de Aminoácidos , Secuencia de Bases , Exones/genética , Femenino , Proteínas de Unión al GTP , Heterogeneidad Genética , Haplotipos/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas de la Membrana , Datos de Secuencia Molecular , Linaje , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Usher syndrome (USH) is characterised by congenital sensorineural hearing loss and progressive pigmentary retinopathy. All three subtypes (USH1, USH2, and USH3) are inherited as recessive traits. People with Usher type 2 (USH2) have normal vestibular responses and moderate to severe hearing loss. These syndromes have been found to be genetically heterogeneous, with a single locus for USH2 at 1q41 (USH2A), six loci for USH1, and one for USH3. Some USH2 families have been excluded from the 1q41 locus suggesting that a second, as yet unidentified, locus (USH2B) must exist. Linkage studies suggest that around 90% of USH2 families are USH2A. Four USH2 families were analysed for linkage to markers flanking the USH2A locus. In one of these families a recombination event was observed in an affected subject which excludes the USH2A gene from proximal to the marker AFM143XF10 and defines this as the new centromeric flanking marker for the USH2A locus. A further recombination event in another patient from this family confirmed AFM144XF2 as the telomeric flanking marker. The interval between these polymorphic markers is estimated to be 400 kb. This region is completely contained in each of three YACs from the CEPH library: 867g9, 919h3, and 848b9. This refinement more than halves the critical genetic interval and will greatly facilitate positional cloning of the USH2A gene.
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Mapeo Cromosómico , Cromosomas Humanos Par 1/genética , Pérdida Auditiva Sensorineural/genética , Retinitis Pigmentosa/genética , Síndrome , Consanguinidad , Proteínas de la Matriz Extracelular/genética , Marcadores Genéticos , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Recombinación GenéticaRESUMEN
Autosomal dominant retinitis pigmentosa (ADRP) is caused by mutations in two known genes, rhodopsin and peripherin/Rds, and seven loci identified only by linkage analysis. Rhodopsin and peripherin/Rds have been estimated to account for 20-31% and less than 5% of ADRP, respectively. No estimate of frequency has previously been possible for the remaining loci, since these can only be implicated when families are large enough for linkage analysis. We have carried out such analyses on 20 unrelated pedigrees with 11 or more meioses. Frequency estimates based on such a small sample provide only broad approximations, while the above estimations are based on mutation detection in much larger clinic based patient series. However, when markers are informative, linkage analysis cannot fail to detect disease causation at a locus, whereas mutation detection techniques might miss some mutations. Also diagnosing dominant RP from a family history taken in a genetic clinic may not be reliable. It is therefore interesting that 10 (50%) of the families tested have rhodopsin-RP, suggesting that, in large clearly dominant RP pedigrees, rhodopsin may account for a higher proportion of disease than had previously been suspected. Four (20%) map to chromosome 19q, implying that this is the second most common ADRP locus. One maps to chromosome 7p, one to 17p, and one to 17q, while none maps to 1cen, peripherin/Rds, 8q, or 7q. Three give exclusion of all of these loci, showing that while the majority of dominant RP maps to the known loci, a small proportion derives from loci yet to be identified.
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Frecuencia de los Genes , Genes Dominantes/genética , Heterogeneidad Genética , Ligamiento Genético , Retinitis Pigmentosa/genética , Mapeo Cromosómico , Femenino , Humanos , Masculino , Mutación , Linaje , Rodopsina/genéticaRESUMEN
OBJECTIVE: Using molecular genetics as the basis for diagnosis, to assess the phenotype in the family originally described as having dominantly inherited Doyne honeycomb retinal dystrophy (DHRD) linked to chromosome 2p16. DESIGN: Clinical examination including fluorescein angiography was undertaken in 107 family members. Nine affected patients underwent electroretinography, perimetry, dark adaptometry, color-contrast sensitivity measurement, and autofluorescent fundus imaging. PATIENTS: The disease-associated haplotype used to allocate disease status was based on our further refinement of the DHRD locus to between loci D2S2739 and D2S378. The study identified 50 affected patients. In addition, previously published information on a further 8 individuals was used. The study population represented 6 generations of a 9-generation pedigree. RESULTS: Three types of deposits were seen: large, soft drusen at the macula and abutting the optic nerve head; small, hard deposits that in some patients radiated from the macula; and autofluorescent deposits. Most younger affected individuals exhibited small hard drusen only at the macula and had normal visual function. Information on 2 patients suggested that DHRD can be a cause of childhood-onset blindness. Advanced disease was associated with severe visual loss and posterior pole atrophy without signs of drusen. Advanced age was not invariably associated with severe visual loss. CONCLUSIONS: Previously identified characteristics of DHRD were confirmed and new features identified. Contrary to previous reports, the constancy and severity of radial (basal laminar) drusen seen clinically are the only features that can be used to differentiate between DHRD and malattia leventinese. The highly variable phenotype suggests that the influence of the DHRD-mutant gene may be modulated by other genetic and/or environmental factors.
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Cromosomas Humanos Par 2/genética , Genes Dominantes/genética , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Adulto , Anciano , Anciano de 80 o más Años , Sensibilidad de Contraste , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Ligamiento Genético , Genotipo , Humanos , Mácula Lútea/patología , Masculino , Persona de Mediana Edad , Disco Óptico/patología , Linaje , Fenotipo , Degeneración Retiniana/fisiopatología , Pruebas del Campo VisualRESUMEN
We previously reported that intravenous injections in rabbits or guinea pigs of divalent antibodies to purified protein or carbohydrate antigens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the injurious effect of subsequent injection of antibodies (adaptation), associated with shedding of antigen-antibody complexes from endothelial cells. In the present study, we investigated and compared in mice the effects of 3-day multiple injections of two different rabbit antibody (IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple antigens of the renal tubular brush border (BB), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which showed loss of DPP IV from cell surface. However, the monoreactive anti-DPP IV IgG induced considerably greater reduction than polyreactive anti-BB IgG. Loss of DPP IV from the cell surface probably occurred by shedding of immune complexes into vascular and extravascular fluids, including bile and urine. The results may have relevance to hyperacute rejection of xenografts, as from pigs to primates. Since human natural antibodies that bind to porcine cells are polyreactive, a new prophylactic strategy for hyperacute rejection might be based on down-regulation of the major xenogeneic antigen, alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl antibodies before transplantation.
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Anticuerpos Monoclonales/farmacología , Dipeptidil Peptidasa 4/metabolismo , Inmunoglobulina G/farmacología , Secuencia de Aminoácidos , Animales , Dipeptidil Peptidasa 4/inmunología , Inmunoglobulina G/metabolismo , Intestino Delgado/enzimología , Riñón/enzimología , Hígado/enzimología , Pulmón/enzimología , Ratones , Datos de Secuencia Molecular , Conejos , Distribución TisularRESUMEN
Degeneration in the macula region of the retina is a feature of a heterogeneous group of inherited, progressive disorders, causing blinding visual impairment. Autosomal dominant Doyne's honeycomb retinal dystrophy (DHRD) is characterised by the presence of drusen deposits at the level of Bruch's membrane in the macula and around the edge of the optic nerve head. We have studied 63 members of a large, nine-generation British pedigree by linkage analysis. Two-point analysis showed significant linkage to nine markers on the short arm of chromosome 2, a region overlapping that recently reported to be linked to Malattia leventinese. A maximum lod score (Zmax) of 7.29 (theta = 0.0) was obtained at marker locus D2S2251. Haplotype analysis of recombination events localised the disease to a 5 cM region between marker loci D2S2316 and D2S378. Striking clinical similarities between DHRD and the more common condition age-related macular degeneration (ARMD) suggest that the disease gene at this locus could be considered as the most likely candidate in future studies on ARMD.
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Mapeo Cromosómico , Cromosomas Humanos Par 2/genética , Genes Dominantes/genética , Degeneración Macular/genética , Femenino , Haplotipos , Humanos , Escala de Lod , Masculino , LinajeRESUMEN
A form of autosomal dominant retinitis pigmentosa (ADRP) mapping to chromosome 17p has been reported in a single large South African family. We now report a new family with severe early onset ADRP which maps to 17p. Linkage and haplotype analysis in this family places the ADRP locus in the 5 cM interval between markers AFMc024za5 and D17S1845, confirming the data obtained in the South African family. The discovery of a second 17p linked family may imply that this is one of the more common loci for dominant RP. In addition, the confirmation of an RP diagnosis at this locus is of interest since loci for a dominant cone dystrophy and Leber's congenital amaurosis (LCA1) have recently been linked to the same markers. While the cone dystrophy locus may be allelic with RP, our data and that of Goliath et al show that distinct genes are responsible for dominant RP and Leber's congenital amaurosis on chromosome 17p.
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Cromosomas Humanos Par 17 , Genes Dominantes , Retinitis Pigmentosa/genética , Femenino , Haplotipos , Humanos , Masculino , Repeticiones de Microsatélite , LinajeRESUMEN
Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.
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Catarata/genética , Mapeo Cromosómico , Cromosomas Humanos Par 17 , Catarata/congénito , Femenino , Genes Dominantes , Ligamiento Genético , Marcadores Genéticos , Humanos , Cristalino/patología , Escala de Lod , Masculino , LinajeRESUMEN
Inherited retinal dystrophies are important causes of blindness in the Western world. Molecular genetic techniques, and the use of large pedigrees exhibiting such conditions, have been instrumental in finding causative disease genes. The genealogy of families with a rare condition known as Doyne's honeycomb retinal degeneration was first described in 1899. Investigating this phenotype is extremely important because of the similarities it shares with age-related macular degeneration, and it may lead us to a gene that is involved in this complex genetic trait. In this paper we review the original genealogy of the families described by Doyne, and explain the methods used to identify the living descendants of these families.