RESUMEN
Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, generally equal in size or smaller than a chromosome 20 of the same metaphase spread. Most of them are unexpectedly detected in routine karyotype analyses, and it is usually not easy to correlate them with a specific clinical picture. A small group of sSMCs is derived from more than one chromosome, called complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based array, and fluorescence in situ hybridization (FISH) were performed to investigate its origin. Array and FISH analyses revealed a der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features commonly found in patients with partial duplication or triplication of 8p and 14q. This is the first report describing a patient with a congenital der(14)t(8;14)(p23.2;q22.1)dn sSMC.
Asunto(s)
Trastornos de los Cromosomas/genética , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 8/genética , Anomalías Múltiples/genética , Preescolar , Bandeo Cromosómico , Trastornos de los Cromosomas/patología , Factores de Transcripción Forkhead/genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Masculino , Reacción en Cadena de la Polimerasa Multiplex , Proteínas del Tejido Nervioso/genética , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
We present a 2-year-old boy with a de novo 46,XY,idic(Y)(q11.221),del(4)(q26q31.1) karyotype. G-banding, FISH, MLPA, and SNP-array techniques were used to characterize the 24-Mb deletion in 4q and the breakpoint in the isodicentric Y-chromosome region between 15,982,252 and 15,989,842 bp. The patient presented with mild facial dysmorphism, hemangioma, mild frontal cerebral atrophy, and Dandy-Walker variant. Essentially, this case reveals that patients can present more complex genomic imbalances than initially suspected.
RESUMEN
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6 percent (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.
Asunto(s)
Femenino , Humanos , Masculino , Heterogeneidad Genética , Ligamiento Genético/genética , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Factor de Crecimiento Transformador beta/genética , Distribución de Chi-Cuadrado , Estudios de Cohortes , Marcadores Genéticos , Escala de Lod , Tasa de Mutación , Síndrome de Marfan/diagnósticoRESUMEN
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.
Asunto(s)
Heterogeneidad Genética , Ligamiento Genético/genética , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Factor de Crecimiento Transformador beta/genética , Distribución de Chi-Cuadrado , Estudios de Cohortes , Femenino , Fibrilina-1 , Fibrilinas , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Síndrome de Marfan/diagnóstico , Tasa de MutaciónRESUMEN
PURPOSE: To investigate the transforming growth factor beta-induced gene (TGFBI) mutations in Brazilian patients with corneal dystrophy and to evaluate the phenotype-genotype correlation in these patients. METHODS: A total of 11 unrelated families were studied. The diagnosis of corneal dystrophy was based on clinical and histopathological findings. Genomic DNA was extracted from peripheral blood leucocytes, and exons 4 and 12 of the TGFBIgene were amplified by polymerase chain reaction followed by direct sequencing on both strands. RESULTS: Five different mutations in the TGFBIgene were found in the probands. We identified the following mutations: lattice corneal dystrophy--R124C and A546T; Reis-Bücklers corneal dystrophy--R555Q and R124L; granular corneal dystrophy--R555W and Avellino dystrophy--R555W. In three of the 11 studied families there was no mutation in exons 4 and 12. CONCLUSIONS: This is the first report of mutations in the TGFBIgene in a series of Brazilian patients with corneal dystrophy. The findings indicate that TGFBIgene screening should be considered in the diagnosis of corneal dystrophy.
Asunto(s)
Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Mutación , Factor de Crecimiento Transformador beta/genética , Secuencia de Bases , Análisis Mutacional de ADN/métodos , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodosRESUMEN
We selected 114 dysmorphic syndromes, and based on published data, have elaborated a general picture, including characteristic clinical, radiological and pathological signs. This database was prepared to run on personal computers. lt is possible to browse or search for the syndromes, features and references, among other characteristics.The dysmorphic syndromes were divided into two different sets, according to their mode of inheritance. The first comprises 78 monogenic syndromes with defined inheritance, while the second comprises 36 presently undefined syndromes with suggested monogenic inheritance. Among the first group, 53 have autosomal recessive inheritance. Although in almost half of the syndromes death is mostly perinatal, longer survival can be found. The organic systems involved among the 114 syndromes studied were as follows: Osteoarticular 81 per cent, cardiovascular 54 per cent, genitourinary 47 per cent, central nervous system 42 per cent, respiratory 41 per cent and gastrointestinal 37 per cent. Abnormalities of the osteoarticular system was the main cause of death in the majority of the syndromes.