Clinical and molecular analysis of human reproductive disorders in Brazilian patients
Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the exp...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2004-01-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2004000100019 |
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| author | A.C. Latronico E.M.F. Costa S. Domenice R.V. Correa M.B.F. Kohek I.J.P. Arnhold B.B. Mendonca |
| author_facet | A.C. Latronico E.M.F. Costa S. Domenice R.V. Correa M.B.F. Kohek I.J.P. Arnhold B.B. Mendonca |
| author_sort | A.C. Latronico |
| collection | DOAJ |
| description | Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHß, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG. |
| first_indexed | 2024-12-11T07:42:55Z |
| format | Article |
| id | doaj.art-67abada65bc5498f9ba0f0ec4d382149 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-11T07:42:55Z |
| publishDate | 2004-01-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-67abada65bc5498f9ba0f0ec4d3821492022-12-22T01:15:31ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2004-01-0137113714410.1590/S0100-879X2004000100019Clinical and molecular analysis of human reproductive disorders in Brazilian patientsA.C. LatronicoE.M.F. CostaS. DomeniceR.V. CorreaM.B.F. KohekI.J.P. ArnholdB.B. MendoncaSeveral genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHß, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2004000100019HypogonadismPubertyGonadotropinsGenetic mutation |
| spellingShingle | A.C. Latronico E.M.F. Costa S. Domenice R.V. Correa M.B.F. Kohek I.J.P. Arnhold B.B. Mendonca Clinical and molecular analysis of human reproductive disorders in Brazilian patients Brazilian Journal of Medical and Biological Research Hypogonadism Puberty Gonadotropins Genetic mutation |
| title | Clinical and molecular analysis of human reproductive disorders in Brazilian patients |
| title_full | Clinical and molecular analysis of human reproductive disorders in Brazilian patients |
| title_fullStr | Clinical and molecular analysis of human reproductive disorders in Brazilian patients |
| title_full_unstemmed | Clinical and molecular analysis of human reproductive disorders in Brazilian patients |
| title_short | Clinical and molecular analysis of human reproductive disorders in Brazilian patients |
| title_sort | clinical and molecular analysis of human reproductive disorders in brazilian patients |
| topic | Hypogonadism Puberty Gonadotropins Genetic mutation |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2004000100019 |
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