ABSTRACT
A point mutation within exon 7 producing an amino acid coding change and a recognition site for the endonuclease Ncol has been reported in the HLA-Bw47-linked CYP21A pseudogene and some mutant CYP21B (steroid 21-hydroxylase) genes of patients with congenital adrenal hyperplasia (CAH). Whether this mutation is deleterious was not demonstrated. We analyzed DNA from various subjects for the presence of the exon 7 Ncol site: group 1, 10 normal subjects; group 2, 11 patients with salt-losing CAH; and group 3, 18 members of an Amish pedigree in which 10 expressed HLA-Bw47 not linked to CAH. Southern blots of Ncol-digested genomic DNA which were hybridized with CYP21 cDNA showed that four subjects of group 1 had a heterozygous Ncol pattern. In group 2, seven patients had the Ncol site; two of them were homozygous for the site and had deletions of both CYP21B genes. The other five were heterozygous for the Ncol site, which was linked to a CYP21B deletion and a HLA-Bw47 haplotype. In group 3, no one exhibited the exon 7 Ncol site. To map the Ncol sites to CYP21A or CYP21B in the normal subjects, DNA from the four Ncol heterozygous subjects was double digested with Ncol and Mbol and hybridized with CYP21 cDNA. Ncol-Mbol fragments unique to CYP21A were identified in all four, but the smaller CYP21B-specific fragments were not detected. Their genomic DNA in the region of exon 7 (bases +1167 to +2058) was then amplified, cloned, and sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Deoxyribonucleases, Type II Site-Specific/metabolism , Exons , Polymorphism, Restriction Fragment Length , Steroid 21-Hydroxylase/genetics , Adrenocorticotropic Hormone , Base Sequence , Chromosome Deletion , Female , HLA-B Antigens/genetics , Heterozygote , Homozygote , Humans , Male , Molecular Sequence Data , Mutation , Polymerase Chain Reaction , Restriction MappingABSTRACT
Adrenocortical carcinoma (ACC), a very rare tumor in children in the United States, is apparently more common among Brazilian children. We reviewed the medical records of 40 children whose disease was diagnosed between 1966 and 1987. There were 12 boys and 28 girls; their median age was 3.9 years (range, 1 day to 15.7 years). Virilization was the most common clinical sign (37 of 40); other signs included abdominal mass, deepened voice, plethora, hypertension, seizures (seven patients) and, rarely, weight loss (two patients). The median time between first signs or symptoms and diagnosis was 1.4 years (range, 3 days to 5 years). Four of 33 tumors were classified as benign according to the Weiss, van Slooten, or Hough systems (tumor tissue was unavailable for seven patients). Tumors were completely resected in 26 of 38 patients; of those, 17 are in continuous complete remission, five relapsed, and four have been lost to follow-up. One patient, who had local recurrence, has been in a third complete remission for 18+ months after tumor resection and chemotherapy (cisplatin and etoposide). Of the remaining 14 patients, 11 died of progressive disease, the diagnosis was confirmed at autopsy in two, and one has been lost to follow-up. Univariate analysis disclosed that age greater than or equal to 3.5 years at diagnosis, interval of greater than or equal to 6 months between first symptoms and diagnosis, tumor weight greater than 100 g, tumor size greater than 200 cm3, and high levels of urinary 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OH) were associated with an unfavorable outcome. Multivariate analysis disclosed that only a tumor size greater than 200 cm3 independently identifies those patients with an unfavorable prognosis. Among the variables known before surgery, age, and the interval between first symptoms and diagnosis were important predictors of outcome. Our data suggest that some children with ACC and certain clinical characteristics are at high risk of primary treatment failure and, therefore, are good candidates for investigational adjuvant therapy.
Subject(s)
Adrenal Cortex Neoplasms/diagnosis , Carcinoma/diagnosis , Adolescent , Adrenal Cortex Neoplasms/mortality , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/therapy , Carcinoma/mortality , Carcinoma/pathology , Carcinoma/therapy , Child , Child, Preschool , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Multivariate Analysis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Prognosis , Survival AnalysisABSTRACT
Avaliamos a incidencia de parasitoses intestinais, bem como os niveis de proteinas totais, albumina e hemoglobina circulantes e o desenvolvimento pondero-estatural de meninos em uma instituicao para menores. A incidencia de parasitoses intestinais entre as criancas foi de 90,2%. As infeccoes helminticas nao eram intensas, conforme a contagem de ovos nas fezes. Os niveis de albumina e proteinas totais nos grupos com infeccao ou nao,eram significativamente mais baixos do que o considerado normal para criancas da mesma faixa etaria. Nao havia diferenca nestes parametros, para criancas com baixa estatura comparadas ao grupo todo. A media da estatura dos casos divididos em grupos etarios estava sempre abaixo do 50o. percentil. Em 19 casos, a estatura encontrava-se abaixo do 3o. percentil.Com os dados apresentados nao podemos concluir que a presenca de parasitas intestinais fosse a unica causa da hipoproteinemia e do deficit estatural observado nas criancas estudadas
