RESUMO
Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans. sporadic and inherited mutations in the human sonic hedgehog (SHH) gene cause 37% of familial HPE. A couple was referred to our unit with a family history of two spontaneous first trimester miscarriages and a daughter with HPE who presented early neonatal death. The father had a repaired median cleft lip, absence of central incisors, facial medial hypoplasia, and cleft palate. Intelligence and a brain CT scan were normal. Direct paternal sequencing analysis showed a novel nonsense mutation (W127X). Facial characteristics are considered as HPE microforms, and the pedigree suggested autosomal dominant inheritance with a variable expression of the phenotype. This study reinforces the importance of an exhaustive evaluation of couples with a history of miscarriages and neonatal deaths with structural defects.
Assuntos
Anormalidades Múltiplas/patologia , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/patologia , Permeabilidade do Canal Arterial/patologia , Permeabilidade do Canal Arterial/cirurgia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Gravidez , Síndrome , Ultrassonografia Pré-Natal , Anormalidades Urogenitais/diagnóstico por imagem , Anormalidades Urogenitais/patologia , Adulto JovemRESUMO
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.
Assuntos
Aberrações dos Cromossomos Sexuais , Síndrome de Turner/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Mosaicismo/genética , Reação em Cadeia da Polimerase , Marcação in Situ com Primers , Cromossomos em Anel , Cromossomo X/genética , Cromossomo Y/genéticaRESUMO
Cytogenetic studies have shown that 40-60% of patients with Ullrich-Turner syndrome (UTS) are 45,X, whereas the rest have structural aberrations of the X chromosome or mosaicism with a second cell line containing a structurally normal or abnormal X or Y chromosome. However, molecular analysis has demonstrated a higher proportion of mosaicism, and studies in different populations have shown an extremely variable frequency of Y mosaicism of 0-61%. We used Southern blot analysis and polymerase chain reaction (PCR) to detect the presence of Ycen, ZFY, SRY, and Yqh in 50 Mexican patients with UTS and different karyotypes to determine the origin of marker chromosomes and the presence of Y sequences. Our results indicated the origin of the marker chromosome in 1 patient and detected the presence of Y sequences in 4 45,X patients. Taken together, we found a 12% incidence of Y sequences in individuals with UTS. The amount of Y-derived material was variable, making the correlation between phenotype and molecular data difficult. Only 1 patient had a gonadoblastoma. We discuss the presence of Y chromosomes or Y sequences in patients with UTS and compare our frequency with that previously reported.