Role of a Founder c.201_202delCT Mutation and New Phenotypic Features of Congenital Lipoid Adrenal Hyperplasia in Palestinians
| Autor: | Israela Lerer, Maha Abdulhadi-Atwan, Wendy K. Chung, Ziva Ben Neriah, Sharon E. Oberfield, Ilene Fennoy, Amy M. Jean, Svetlana Ten, Harry J. Hirsch, George Stratigopoulos, Amrit Bhangoo, Karen Meir, David Zangen |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Genotype Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) medicine.disease_cause Biochemistry Endocrinology Internal medicine Testis medicine Humans Child Mutation Adrenal Hyperplasia Congenital business.industry Steroidogenic acute regulatory protein Biochemistry (medical) Infant Newborn Infant Phosphoproteins Phenotype Founder Effect Arabs Pedigree Placental alkaline phosphatase Child Preschool Female business Chromosomes Human Pair 8 Hormone Founder effect |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 92:4000-4008 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2007-1306 |
| Popis: | Congenital lipoid adrenal hyperplasia (CLAH), caused by mutations in steroidogenic acute regulatory protein (StAR), is most frequent in Japanese and Palestinians. We report eight Palestinians from four unrelated families with CLAH.The objective of the study was to identify the mutation(s) in StAR, correlate genotype with phenotype, and determine whether the common mutation represents a founder mutation.Clinical, histopathological, and molecular genetic characterization was performed in these eight patients.All affected individuals (three XY, five XX) presented neonatally with undetectable adrenocortical hormones and are responding to replacement therapy. Only two sisters had neurodevelopmental deficits. Histopathological findings of excised XY gonads included accumulation of fat in Leydig cells. Significantly, already at 1 yr of age, positive placental alkaline phosphatase and octamer binding transcription factor staining indicated neoplastic potential. Sequence analysis of StAR revealed homozygosity for c.201_202delCT mutation in all eight cases, causing premature termination of the StAR protein. This mutation was confirmed to be a founder mutation using both an intragenic microsatellite and several single nucleotide polymorphism markers. Screening of 100 normal Jerusalem Palestinians detected no carriers of this mutation.CLAH is rare in the general Palestinian population. In most Palestinian cases, a founder c.201_202delCT mutation in StAR is the cause. The observed early neonatal presentation may reflect the major StAR protein truncation caused by this mutation. A crucial role for StAR in the central nervous system was not supported with normal neurological examinations in six of eight cases. Finally, we advocate early gonadectomy in XY CLAH cases, given the early onset of neoplastic changes observed histologically. |
| Databáze: | OpenAIRE |
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