ABSTRACT
Familial acromegaly may occur as an isolated pituitary disorder or as a feature of hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1) or the Carney complex. Herein, we characterized a newly identified kindred with isolated acromegaly and searched for germline mutation in genes that have been associated with endocrine tumors [i.e. MEN1, Gs alpha (GNAS1), and Gi2 alpha (GNAI2)], as well as the GHRH receptor (GHRH-R) gene. Genomic DNA was used to amplify exons 2-10 of MEN1, followed by dideoxy fingerprinting mutation analysis and direct sequencing. The GHRH-R gene was analyzed via direct sequencing of PCR-amplified fragments representing the coding exons and intron-exon junctions. To exclude mutation at hot spot areas of GNAS1 and GNAI2, exons 8 and 9 of GNAS1 and exons 5 and 6 of GNAI2 were amplified and screened for mutation via denaturing gradient gel electrophoresis. No mutations were detected in any of the four genes. The present data extend prior reports of the absence of mutation in MEN1, GHRH-R, and GNAS1 and describe the first family with isolated acromegaly in which germline mutation in GNAI2 has been searched.
Subject(s)
Acromegaly/genetics , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , GTP-Binding Protein alpha Subunits, Gs/genetics , Multiple Endocrine Neoplasia Type 1/genetics , Proto-Oncogene Proteins/genetics , Receptors, Neuropeptide/genetics , Receptors, Pituitary Hormone-Regulating Hormone/genetics , Adult , Female , GTP-Binding Protein alpha Subunit, Gi2 , Humans , Male , Nuclear Family , Polymerase Chain ReactionABSTRACT
Activating mutations of the G protein genes have been associated with the development of several endocrine neoplasms. Such activating mutations, gip2, affecting the alpha-subunit of the G alpha i2 protein were previously described by a single group in 30% of ovarian sex cord stromal tumors. Other activating mutations of the alpha-subunit of the Gs (gsp) have been identified in GH-secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and all affected McCune-Albright tissues, but not in sex cord stromal tumors. In the present study, we investigated the presence of gip2 and gsp mutations in 14 human sex cord stromal tumors. Six Leydig cell tumors (4 ovaries and 2 testes), 2 thecomas, 2 granulosa cell tumors, 3 androblastomas, and 1 gonadoblastoma (sex cord and germ cell) were included in this study. Genomic DNA was obtained from either fresh-frozen tumor tissues or paraffin-embedded sections and in some cases from blood samples. Using PCR, denaturing gradient gel electrophoresis, and direct sequencing, we detected 4 tumors (66.6%) with the gsp mutation (R201C) in our series of ovarian and testicular Leydig cell tumors. In contrast, no gip2 mutations were found in any of the sex cord stromal tumors studied. In conclusion, our findings suggest that the putative oncogene gsp may play a significant role in the molecular mechanism of these tumors.
Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go , GTP-Binding Protein alpha Subunits, Gs/genetics , GTP-Binding Proteins/genetics , Leydig Cell Tumor/genetics , Mutation , Ovarian Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Adolescent , Adult , Child , DNA, Neoplasm/analysis , Electrophoresis, Agar Gel , Exons , Female , GTP-Binding Protein alpha Subunit, Gi2 , Humans , Male , Middle Aged , Polymerase Chain Reaction , Sequence Analysis, DNA , Stromal CellsABSTRACT
Samples of cerebrospinal fluid from 103 patients with aseptic meningitis were tested by PCR for detection of leptospires, and the results were compared with those of the microscopic agglutination test (MAT) and an enzyme-linked immunosorbent assay for detection of immunoglobulin M (ELISA-IgM). Of these samples, 39.80% were positive by PCR and 8.74 and 3.88% were positive by MAT and ELISA-IgM, respectively.
Subject(s)
Leptospira/isolation & purification , Leptospirosis/cerebrospinal fluid , Meningitis, Aseptic/cerebrospinal fluid , Adolescent , Adult , Age Distribution , Child , Child, Preschool , DNA, Bacterial/analysis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Leptospirosis/complications , Male , Meningitis, Aseptic/complications , Meningitis, Aseptic/microbiology , Middle Aged , Polymerase Chain Reaction/methodsSubject(s)
Disorders of Sex Development/genetics , Gynecomastia/etiology , Oxidoreductases/deficiency , Adolescent , Adult , Cholestenone 5 alpha-Reductase , Dihydrotestosterone/blood , Disorders of Sex Development/blood , Disorders of Sex Development/diagnosis , Estradiol/blood , Gender Identity , Humans , Male , Testosterone/bloodABSTRACT
Foi realizado estudo clinico, citogenetico histologico e da secrecao hormonal em dois casos de hermafroditismo verdadeiro (HV).O primeiro paciente apresentava cariotipo XX e o segundo XX/XY, sendo os dois antigeno HY positivo. O exame histologico revelou ovotestis no primeiro caso com presenca de espermatogonias ate agora nao descritas no HV. O segundo paciente apresentava ovario histologicamente normal e testiculo com areas de hialinizacao tubular. A avaliacao hormonal no paciente 1 revelou grandes flutuacoes dos niveis de LH, FSH, estradiol e progesterona. Os dois pacientes apresentavam baixa resposta testicular ao estimulo com gonadotrofina corionica e liberacao de LH apos uso de estrogeno semelhante a observada no ser feminino.O citrato de clomifeno induziu resposta ovulatoria no caso testado, podendo ser utilizado na identificacao da presenca de ovotestis em caso de suspeita de HV
