Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
| Autor: | Gema Grau, Luis Castaño, Francisco Rivas-Crespo, Gustavo Pérez-Nanclares, Joaquin Fernández-Toral, Ignacio Diez, Amaia Rodríguez Estévez, Juan Pedro López-Siguero |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Delayed puberty
Male Pediatrics medicine.medical_specialty Adolescent Hydrocortisone Endocrinology Diabetes and Metabolism Genetic counseling Gene mutation Endocrinology Adrenocorticotropic Hormone Hypogonadotropic hypogonadism Internal medicine X-linked adrenal hypoplasia congenita Adrenal insufficiency Medicine Humans Genetic Testing Child Aldosterone Genetic testing medicine.diagnostic_test business.industry DAX-1 Orphan Nuclear Receptor Infant Newborn Infant Genetic Diseases X-Linked medicine.disease Pedigree Hypoadrenocorticism Familial Child Preschool Pediatrics Perinatology and Child Health DAX1 medicine.symptom business Adrenal Insufficiency |
| Zdroj: | Journal of pediatric endocrinologymetabolism : JPEM. 28(9-10) |
| ISSN: | 2191-0251 |
| Popis: | BACKGROUND X-linked adrenal hypoplasia congenita (AHC) is caused by NR0B1 (DAX1) gene mutations. Affected male children suffer from adrenal insufficiency, leading to a salt-wasting crisis in early infancy and hypogonadotropic hypogonadism in adulthood. OBJECTIVE To characterize clinically and at the molecular level a cohort of Spanish patients with AHC. PATIENTS AND METHODS Nine boys (from five families) with AHC were screened for NR0B1 mutations. Clinical and endocrine evaluations were recorded. RESULTS NR0B1 gene mutations were found in all analyzed patients, one of them being novel (p.Gln305*). One patient presented with preserved hypothalamic-pituitary-gonadal axis. Salt-wasting episodes, delayed puberty, and hypogonadotropic hypogonadism were common, although no association was observed between AHC phenotype and genetic mutations. None of the patients has had descendants. CONCLUSIONS AHC phenotype cannot be predicted based on genetic results as there is no definite genotype-phenotype relationship, including intrafamilial variability. Nevertheless, genetic testing for NR0B1 mutations is indicated if there is a suspicion of an X-linked adrenal insufficiency in order to proceed with the appropriate therapy and genetic counseling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|