Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroidogenic acute regulatory protein (StAR) plays a crucial role in the transport of cholesterol from the cytoplasm to the inner mitochondrial membrane, facilitating its conversion to pregnenolone by cytochrome P450scc. Its essential role in steroidogenesis was demonstrated after observing that StAR gene mutations gave rise to a potentially lethal disease named congenital lipoid adrenal hyperplasia, in which virtually no steroids are produced. We report here a 2-month-old female patient, karyotype 46XY, who presented with growth failure, convulsions, dehydration, hypoglycemia, hyponatremia, hypotension, and severe hyperpigmentation suggestive of adrenal insufficiency. Serum cortisol, 17OH-progesterone, dehydroepiandrosterone sulfate, testosterone, 17OH-pregnenolone, and aldosterone levels were undetectable in the presence of high ACTH and plasma renin activity levels. Immunohistochemical analysis of testis tissues revealed the absence of StAR protein. Molecular analysis of StAR gene demonstrated a homozygous G to T mutation within the splice donor site of exon 1 (IVS1 + 1G>T). Her parents and one brother were heterozygous for this mutation. In vitro analysis of the mutation was performed in COS cells transfected with minigenes coding regions spanning exon-intron 1 to 3 carrying the mutant and the wild-type sequences. RT-PCR analyses of the mutant gene showed an abnormal mRNA transcript of 2430 bp (normal size 433 bp). Sequence analysis of the mutant mRNA demonstrated the retention of intron 1. Immunolocalization of the StAR minigene product detected the peptide in the mitochondria of COS cells transfected with the wild-type minigene but not in those transfected with the mutant minigene. We conclude that this mutation gives rise to a truncated StAR protein, which lacks an important N-terminal region and the entire lipid transfer domain.
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PMID:Congenital lipoid adrenal hyperplasia caused by a novel splicing mutation in the gene for the steroidogenic acute regulatory protein. 1476 19

Lipoid congenital adrenal hyperplasia (LCAH) (OMIM No. 201710) is the most severe type of congenital adrenal hyperplasia (CAH). Its clinical presentation includes lethal disturbance of adrenal and gonadal steroid synthesis due to impairment in the conversion of cholesterol to pregnenolone. Infants with this disorder experience salt loss, and glucocorticoid and mineralocorticoid deficiencies. Replacement therapy has enabled long-term survival. Classic LCAH is relatively common in Japan and Korea but extremely rare in Caucasian populations. An XY male 5-year-old child presented at Endocrine Clinic of Armed Forces Institute of Pathology with ambiguous genitalia and hyperpigmentation. He had family history of CAH. His laboratory investigations revealed normal serum cortisol and 17 Hydroxy (17 OH) progesterone levels with high plasma ACTH and renin levels. He had low aldosterone with inadequate response with hCG stimulation test. This is the first case of non-classic LCAH reported in the Pakistani population. Steroidogenic acute regulatory protein (StAR) gene mutations result in LCAH and the condition should be considered in the differential diagnosis of an XY child with primary adrenal insufficiency.
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PMID:A Child with Ambiguous Genitalia: An Atypical Presentation. 3114 23