RESUMO
OBJECTIVE: To investigate the presence of mutations in the open reading frame (ORF), as well as on the 5' and 3', flanking regions of the SRY gene in patients with mixed gonadal dysgenesis (MGD) or with Turner syndrome (TS) and Y mosaicism. STUDY DESIGN: We studied 13 patients with MGD and three patients with TS and Y mosaicism. DNA was isolated from blood leukocytes for subsequent polymerase chain reaction (PCR) and direct sequencing were performed in the ORF, as well as from the 5' and 3' flanking regions of the SRY gene. RESULTS: No mutations were present in any of the patients studied. CONCLUSION: The absence of mutations in these regions indicated that mutations were an unlikely cause of MGD or TS with Y mosaicism and suggested that there are others genes playing an important role in sex development.
Assuntos
Cromossomos Humanos Y/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Disgenesia Gonadal Mista/genética , Mosaicismo/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Síndrome de Turner/genética , Adolescente , Adulto , Criança , Pré-Escolar , DNA/sangue , Humanos , Lactente , Leucócitos/química , Masculino , Fases de Leitura Aberta/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Proteína da Região Y Determinante do SexoRESUMO
OBJECTIVES: To determine the prevalence of chromosomal abnormalities in fetuses with open neural tube defects (NTD) undergoing prenatal chromosome analysis. The role of prenatal ultrasound in detecting those with an underlying chromosomal abnormality was also investigated. METHODS: Over a 6-year period, 144 fetuses with open NTD underwent prenatal chromosome analysis between 12 and 37 weeks of gestation, as part of a prospective, multicenter prenatal diagnosis and counseling program in Chile. This population included 66 fetuses with spina bifida, 46 with acrania/anencephaly, 21 with cephalocele and 11 with iniencephaly. A confident prenatal diagnosis was made in 143 fetuses (99%) and confirmed postnatally in all cases. RESULTS: An underlying chromosomal abnormality was diagnosed in 10 fetuses (7%), six with spina bifida, three with cephalocele and one with craniorachischisis. The prevalence of chromosomal abnormality varied according to the defect present in the fetus, with a 14% (3/21) prevalence among those with cephalocele, 9% (6/66) among those with spina bifida and 2% (1/57) among those with lethal defects such as acrania, anencephaly or iniencephaly. Karyotype results revealed trisomy 18 in seven cases, trisomy 13 in two and mosaicism for a marker chromosome in one. Prenatal ultrasound before the procedure showed that all chromosomally abnormal fetuses had additional findings. The prevalence of chromosomal abnormality in fetuses with spina bifida and cephalocele was higher when chromosome analysis was performed at or before 24 weeks of gestation in comparison to those performed after 24 weeks (5/31 (16%) vs. 4/56 (7%), respectively). However, this difference did not reach statistical significance, probably due to the small number of cases. CONCLUSIONS: A significant number of fetuses with open NTD are chromosomally abnormal. Although prenatal chromosome analysis should be considered in all cases, prenatal ultrasound seems effective in identifying those fetuses with an underlying chromosomal abnormality.
Assuntos
Aberrações Cromossômicas/embriologia , Defeitos do Tubo Neural/embriologia , Ultrassonografia Pré-Natal/métodos , Adulto , Anencefalia/diagnóstico por imagem , Anencefalia/embriologia , Anencefalia/epidemiologia , Chile/epidemiologia , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Feminino , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Mosaicismo/genética , Defeitos do Tubo Neural/diagnóstico por imagem , Defeitos do Tubo Neural/epidemiologia , Gravidez , Prevalência , Estudos Prospectivos , Disrafismo Espinal/diagnóstico por imagem , Disrafismo Espinal/embriologia , Disrafismo Espinal/epidemiologia , Trissomia/genéticaRESUMO
We report here on two mosaic patients with both an idic(Yp) and a microchromosome. FISH with the DYZ3 alphoid repeat demonstrated that the isodicentrics effectively exhibited two alphoid clusters whereas the small markers had a Y-centromere. These data, along with 4 previous observations, indicate that such microchromosomes effectively result from functional dicentricity of isodicentric Y-chromosomes and represent the excision of one centromere plus various amounts of adjacent chromatin. Other than a real infrequency of such a concurrence or a very low proportion of the cell line(s) containing the microchromosome, the paucity of observations points to a high rate of underdiagnosis as revealed by two idic(Y) instances in which the microchromosome was detected only in samples assessed by FISH.
Assuntos
Cromossomos Humanos Y/genética , Mosaicismo/genética , Síndrome de Turner/genética , Diagnóstico Diferencial , Humanos , Recém-Nascido , Cariotipagem , Metáfase/genéticaRESUMO
BACKGROUND: The phenotypic expression of an additional chromosome 9 causes a very broad clinical spectrum of anomalies. The prognosis for infants with non-mosaic tetrasomy 9p is poor, and they usually die at a very early age. CASE: In this article we present a new case of complete tetrasomy 9p in a newborn girl with multiple dysmorphologic features. Cytogenetic studies were carried out by CBG, GTG, and QFQ chromosome bandings, as well as by fluorescence in situ hybridization (FISH). The cytogenetic findings for the newborn girl showed an extra chromosome interpreted as an isochromosome 9p. The karyotype was characterized as 47,XX,+mar.ish i(9)(p10)(wcp9+). The parental chromosomes were normal. CONCLUSIONS: The karyotype and clinical features of the newborn girl (e.g., typical craniofacial dysmorphism, severe skeletal anomalies, and visceral and genito-urinary malformations), compared with cases reported in the literature, give additional support to a clinical definition of this chromosomal syndrome.
Assuntos
Anormalidades Múltiplas/genética , Aneuploidia , Cromossomos Humanos Par 9 , Mosaicismo/genética , Anormalidades Múltiplas/patologia , Bandeamento Cromossômico , Evolução Fatal , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Idade Materna , Gravidez de Alto RiscoRESUMO
Due to the presence of two different clones of cells in early embryogenesis, numerous congenital and acquired dermatoses have a linear distribution following the lines of Blaschko. Acquired inflammatory skin diseases are rarely observed in linear patterns. Our patient was born with macrocephaly, left eye glaucoma, and a left facial and contralateral corporal hemihypertrophy, cerebral dysgenesis, and skeletal abnormalities. Hypopigmented S-shaped linear macules on the trunk and linear streaks on the arms and legs were compatible with hypomelanosis of Ito. At 5 years of age the patient presented with an erythematous follicular exanthem compatible with scarlet fever exclusively in the lines of Blaschko. This fact suggests a genetic mosaicism.
Assuntos
Exantema/complicações , Hipopigmentação/complicações , Hipopigmentação/genética , Mosaicismo/genética , Infecções Estreptocócicas/complicações , Streptococcus pyogenes/isolamento & purificação , Pré-Escolar , Exantema/tratamento farmacológico , Exantema/genética , Feminino , Humanos , Penicilinas/uso terapêutico , Fenômenos Fisiológicos da Pele/genética , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/genéticaRESUMO
Es conocido que pacientes con trastornos severos de la espermatogénesis presentan alteraciones cromosómicas. En el brazo largo del cromosoma Y se encuentran los genes vinculados con la formación de gametas, por lo que deleciones en esta región del cromosoma son la causa de azoospermia u oligospermia severa. Dichas deleciones pueden presentarse en todas las líneas celulares o bien sólo en algunas de ellas, evidenciándose en línea pura o en mosaico con una línea 45,X en distintos porcentajes, lo que condiciona la variabilidad en la expresión del fenotipo. Este estudio tiene como objetivo correlacionar el fenotipo y el cariotipo en pacientes infértiles con diferenciación sexual masculina. El estudio cromosómico efectuado en tres pacientes puso en evidencia dos líneas celulares (mosaicismo), una de ellas 45,X y otra 46,X del (Y) (q11). Desde el punto de vista clínico, dos pacientes que presentaban la línea celular a 45,X en muy bajo porcentaje (3 y 5 por ciento) presentaban talla baja, no familiar, (uno con estigmas turnerianos, cuello y cuarto metacarpiano corto), vello escaso y disminución del volumen testicular. El tercer paciente cuya línea 45,X se encontró en un 32 por ciento, la única expresión fenotípica fue inecomastia bilateral. Los tres casos cursaron con niveles de FSH elevados en forma basal o en respuesta al estímulo con GnRH, pero sólo el paciente con estigmas turnereanos presentó niveles elevados de estradiol sérico. Además de lo mencionado sobre los genes de la espermatogénesis en el brazo largo del Y, también se encuentran aquello que intervienen en la talla, dismorfias y retraso madurativo. La variabilidad de expresión en estos tres pacientes pone en evidencia que otros factores independientes de la línea 45,X tienen implicancias en la expresión de su fenotipo (AU)
Assuntos
Humanos , Masculino , Adulto , Mosaicismo/genética , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Deleção Cromossômica , Citogenética , FenótipoRESUMO
Lymphocyte cultures from five patients with chromosomal mosaicism (two 47,XY,+21/46,XY, one 47,XX,+21/46,XX, one 45,X/46,XX, and one 47,XXY/46,XY) were studied using sister chromatid differential staining technique for cell kinetic evaluation. Aneuploid and normal cell lines were compared to identify changes in cellular proliferation in vitro that could be related to cellular selective advantage and cell-line-proportion changes occurring with age. Comparison of the percentage of cells in different cell generations in 48, 72, and 96 h-cultures shows no differences between the aneuploid and normal cell lines indicating that cell-cycle kinetics is similar in these cells in vitro.
Assuntos
Ciclo Celular , Transtornos Cromossômicos/genética , Mosaicismo/genética , Aneuploidia , Células Cultivadas , Pré-Escolar , Cromátides/genética , Diploide , Síndrome de Down/genética , Frequência do Gene/genética , Humanos , Lactente , Cariotipagem , Cinética , Síndrome de Klinefelter/genética , Linfócitos/metabolismo , Metáfase , Probabilidade , Síndrome de Turner/genéticaRESUMO
FRAXE (FMR2) is a fragile site associated with mental impairment located in Xq28, 600 kb distal to FRAXA (FMR1), the fragile X syndrome fragile site. The FRAXE mutation is an expansion of a CCG repeat that results in methylation of a nearby CpG island. FRAXE alleles could be divided into four categories: normal (6-30 CCG repeats), intermediate (31-60 CCG repeats), premutation (61-200 CCG repeats), and full mutation (over 200 repeats). We have developed a non-isotopic polymerase chain reaction (PCR)-based assay for the identification of FRAXE full mutation alleles among mentally impaired men. In this novel PCR test for the FRAXE locus, we used three primers to permit an amplification of a 223 bp monomorphic internal control fragment in addition to the amplification of a 419 bp (CCG)(16) FRAXE locus band. A linear series of 93 male patients referred for FRAXE testing but found to be negative for the (CCG)(n) expansion in the FMR2 gene by Southern blotting analysis were retested by our PCR technique. In addition, we analyzed two positive controls consisting of a FRAXE fully mutated male and one male with a Xq terminal deletion. The developed PCR test showed accuracy of 100% in the normal individuals retested by PCR analysis, as well as in the two positive control samples utilized, in which the strategy of multiplex amplification worked as expected. Although not suitable for medical diagnosis of females and mosaics, it constitutes an important strategy for PCR typing and for FRAXE population screening.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Testes Genéticos/métodos , Deficiência Intelectual/genética , Mutação/genética , Proteínas Nucleares/genética , Transativadores/genética , Alelos , Southern Blotting , Ilhas de CpG/genética , Síndrome do Cromossomo X Frágil/diagnóstico , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Dados de Sequência Molecular , Mosaicismo/genética , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
Among the various types of pigmentary disturbances associated with mosaicism, the phylloid pattern (Greek phyllon = leaf, eidos = form) is characterized by multiple leaf-like patches reminiscent of an art nouveau painting. The number of cases displaying this unusual pattern is so far limited. We describe a phylloid pattern of hypomelanosis in a 3-year-old girl with multiple congenital anomalies including microcephaly, midfacial hypoplasia, cleft lip, coloboma, posteriorly rotated ears, pectus carinatum, and pronounced mental and physical retardation. In addition, this child had oval or oblong patches of hyperpigmentation involving the trunk in a horizontal arrangement dissimilar from the phylloid hypomelanotic pattern. In peripheral blood lymphocytes a karyotype 46,XX,-13,+t(13q;13q) was consistently found, whereas cultured skin fibroblasts showed a complex form of mosaicism comprising three different abnormal cell lines (46,XX,-13,+t(13q;13q)/45,XX,-13/45,XX,-13,+frag). This case provides further evidence that the phylloid pattern represents a separate category of pigmentary disturbance to be distinguished from other types of cutaneous mosaicism such as the lines of Blaschko or the checkerboard arrangement.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 13 , Hipopigmentação/genética , Melaninas/deficiência , Melanose/genética , Mosaicismo/genética , Adulto , Pré-Escolar , Citogenética , Feminino , Humanos , Hipopigmentação/patologia , Pele/patologia , Cromossomo XRESUMO
According to cytogenetic analysis, about 50% of Turner individuals are 45,X. The remaining cases have a structurally abnormal X chromosome or are mosaics with a second cell line containing a normal or abnormal sex chromosome. In these mosaics, approximately 20% have a sex marker chromosome whose identity cannot usually be determined by classical cytogenetic methods, requiring the use of molecular techniques. Polymerase chain reaction (PCR), primed in situ labeling (PRINS), and fluorescence in situ hybridization (FISH) analyses were performed in 8 patients with Turner syndrome and 45,X mosaic karyotypes to determine the origin and structure of the marker chromosome in the second cell line. Our data showed that markers were Y-derived in 2 patients and X-derived in the remaining 6 patients. We were also able to determine the breakpoints in the two Y chromosomes. The use of cytogenetic and molecular techniques allowed us to establish unequivocally the origin, X or Y, of the marker chromosomes in the 8 patients with Turner phenotype. This study illustrates the power of resolution and utility of combined cytogenetic and molecular approaches in some clinical cases.