RESUMO
An assay for ataxia-telangiectasia (A-T) heterozygotes, i.e., healthy carriers of the A-T gene(s), requiring only a small sample (3.5 mL) of peripheral blood, is described. Frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes collected by demecolcine from 0.5 hour to 1.5 hours after x irradiation with 58 roentgens were twofold to threefold higher in A-T heterozygotes than in clinically normal controls and twofold to three-fold higher in A-T patients (homozygotes) than in A-T gene carriers. The persistence of chromatid breaks and gaps in lymphocytes following radiation-induced DNA damage during G2 suggests a deficiency or deficiencies in DNA repair that may be the defect at the molecular level that results in the enhanced radiosensitivity and cancer proneness characterizing A-T gene carriers and patients.
Assuntos
Ataxia Telangiectasia/genética , Cromátides/efeitos da radiação , Dano ao DNA , Interfase/efeitos da radiação , Adolescente , Adulto , Idoso , Criança , Feminino , Heterozigoto , Humanos , Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Tolerância a RadiaçãoRESUMO
Although girls with Turner's syndrome (45,X) are not at risk for malignancy, patients with feminizing testicular syndrome with XY chromosome composition and patients with "mixed gonadal dysgenesis" are at risk for malignancy, and bilateral gonadectomy is performed. We have treated seven girls with "Turner-like" syndrome, who we believe are also "at risk" for development of malignancy and in whom gonadectomy should be performed. We present seven cases of phenotypically typical females, without sexual ambiguity, who presented with primary amenorrhea and short stature (5) and/or minor dysmorphic features (2). Chromosome analysis showed 45,X karyotype plus a fragment that we could not rule out as being part of a Y chromosome (in one patient a complete Y chromosome). In two patients, the fragment was subsequently positively identified as a Y, using a DNA probe. In view of the known high incidence of development of gonadoblastoma in the dysgenetic gonads of phenotypic females with a Y chromosome, bilateral gonadectomy was performed in these girls. Bilateral genital streaks with normal uterus and Fallopian tubes were found in all patients. In two patients unsuspected gonadoblastoma, without metastases, was found. In five cases, Leydig cells and tubular structures resembling rete testes were found, cells that are associated with Y-chromosomal tissue. We stress the need for complete chromosomal evaluation of phenotypically female patients with primary amenorrhea or features of Turner's syndrome. If a Y chromosome or the possibility of a Y chromosome cannot be excluded, gonadectomy should be performed because of the risk of malignancy.
Assuntos
Disgerminoma/etiologia , Disgenesia Gonadal 46 XY/complicações , Neoplasias Ovarianas/etiologia , Síndrome de Turner/complicações , Adolescente , Amenorreia/etiologia , Criança , Pré-Escolar , Sondas de DNA , Disgerminoma/genética , Disgerminoma/patologia , Disgerminoma/cirurgia , Feminino , Disgenesia Gonadal 46 XY/genética , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Fatores de Risco , Síndrome de Turner/genética , Síndrome de Turner/patologiaRESUMO
Gardner syndrome is a dominantly inherited familial cancer syndrome characterized by intestinal polyposis, bony hamartomata, and various soft tissue tumors. The risk of malignancy during adult life is essentially 100%, but as yet no phenotypic marker nor biochemical or serological linkage have been useful to identify the presence of the gene in early life. We studied three families in which multiple and bilateral patches of congenital hypertrophy of the retinal pigment epithelium are related uniquely to other phenotypic features of the Gardner gene. This readily identifiable characteristic may be useful to identify early in life individuals at risk for malignancy. We also suggest that the Gardner syndrome may be genetically heterogeneous.