Alu Sx repeat-induced homozygous deletion of the StAR gene causes lipoid congenital adrenal hyperplasia
| Autor: | Stefan A. Wudy, Huy-Hoang Nguyen, Frank Hannemann, Rita Bernhardt, Antje Eiden-Plach, Michaela F. Hartmann, Ursula Schneider |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Fludrocortisone Lipoid congenital adrenal hyperplasia Clinical Biochemistry Molecular Sequence Data Alu element Biology Biochemistry Primary Adrenal Insufficiency chemistry.chemical_compound Exon Endocrinology Alu Elements Internal medicine medicine Humans Metabolomics Cholesterol Side-Chain Cleavage Enzyme Allele Molecular Biology Gene Sequence Deletion Genetics Aldosterone Disorder of Sex Development 46 XY Adrenal Hyperplasia Congenital Base Sequence Homozygote Cell Biology medicine.disease Phosphoproteins Pedigree chemistry Molecular Medicine Female medicine.drug |
| Zdroj: | The Journal of steroid biochemistry and molecular biology. 130(1-2) |
| ISSN: | 1879-1220 |
| Popis: | Lipoid congenital adrenal hyperplasia (Lipoid CAH) is the most severe form of the autosomal recessive disorder CAH. A general loss of the steroid biosynthetic activity caused by defects in the StAR gene manifests as life-threatening primary adrenal insufficiency. We report a case of Lipoid CAH caused by a so far not described homozygous deletion of the complete StAR gene and provide diagnostic results based on a GC-MS steroid metabolomics and molecular genetic analysis. The patient presented with postnatal hypoglycemia, vomiting, adynamia, increasing pigmentation and hyponatremia. The constellation of urinary steroid metabolites suggested Lipoid CAH and ruled out all other forms of CAH or defects of aldosterone biosynthesis. After treatment with sodium supplementation, hydrocortisone and fludrocortisone the child fully recovered. Molecular genetic analysis demonstrated a homozygous 12.1 kb deletion in the StAR gene locus. The breakpoints of the deletion are embedded into two typical genomic repetitive Alu Sx elements upstream and downstream of the gene leading to the loss of all exons and regulatory elements. We established deletion-specific and intact allele-specific PCR methods and determined the StAR gene status of all available family members over three generations. This analysis revealed that one of the siblings, who died a few weeks after birth, carried the same genetic defect. Since several Alu repeats at the StAR gene locus increase the probability of deletions, patients with typical symptoms of lipoid CAH lacking evidence for the presence of both StAR alleles should be analyzed carefully for this kind of disorder. |
| Databáze: | OpenAIRE |
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