Bilateral laparoscopic adrenalectomy for congenital adrenal hyperplasia with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1
| Autor: | Olivier Chabre, Edmond M. Chambaz, Josiane Vivier, Philippe Chaffanjon, Panagiotis Liakos, Yves Morel, Stéphanie Portrat-Doyen, G. Defaye, Françoise Labat-Moleur |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Disorders of Sex Development Biochemistry Exon Endocrinology Adrenocorticotropic Hormone Internal medicine Mineralocorticoids Adrenal Glands Renin medicine Humans Congenital adrenal hyperplasia Steroid 11-beta-hydroxylase Transversion Glucocorticoids Adrenal Hyperplasia Congenital Base Sequence business.industry Reverse Transcriptase Polymerase Chain Reaction Adrenalectomy Biochemistry (medical) Alternative splicing Exons Androgen medicine.disease Alternative Splicing Hypertension Mutation Steroid 11-beta-Hydroxylase Female Laparoscopy business Glucocorticoid medicine.drug |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 85(11) |
| ISSN: | 0021-972X |
| Popis: | We present an in vivo and in vitro study of congenital adrenal hyperplasia in a patient with 11β-hydroxylase deficiency. Sequencing of the CYP11B1 gene showed two new base substitutions, a conservative 954 G→C transversion at the last base of exon 5 (T318T), and a IVS8 + 4A→G transition in intron 8. In addition, two polymorphisms were found in exons 1 and 2. The genetically female patient was raised as a male because of severe pseudohermaphroditism. Glucocorticoid-suppressive treatment encountered difficulties in equilibration and compliance, resulting in uncontrolled hypertension with pronounced hypertrophic cardiomyopathy. At 42 yr of age the occurrence of central retinal vein occlusion with permanent loss of left eye vision led to the decision to perform bilateral laparoscopic adrenalectomy. Surgery was followed by normalization of blood pressure and good compliance with glucocorticoid and androgen substitutive therapies. In vitro, adrenal cells in culture and isolated mitochondria showed extremely low 11β-hydroxylase activity. Analysis of adrenal CYP11B1 messenger ribonucleic acid (mRNA) by RT-PCR and sequencing showed the expression of a shorter mRNA that lacked exon 8 and did not contain either the exon 5 mutation or the exon 1 and 2 polymorphisms. This suggested that one CYP11B1 allele carried the intron 8 mutation, responsible for skipping exon 8. The other allele carried the exon 5 mutation, and its mRNA was not detectable. Western blot analysis showed weak expression of a shorter CYP11B immunoreactive band of 43 kDa, consistent with truncation of exon 8. Thus, bilateral adrenalectomy in this patient allowed effective treatment of severe hypertension and helped in understanding the mechanisms and physiopathological consequences of two novel mutations of CYP11B1. |
| Databáze: | OpenAIRE |
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