scholarly journals A Novel Mutation of the Steroidogenic Acute Regulatory Protein (StAR) Gene in a Japanese Patient with Congenital Lipoid Adrenal Hyperplasia

2008 ◽  
Vol 17 (1) ◽  
pp. 23-25
Author(s):  
Katsura Ishizu ◽  
Junko Tsubaki ◽  
Wakako Jyo ◽  
Toshihiro Tajima
Keyword(s):  
Japanese Patient ◽  
Novel Mutation ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Adrenal Hyperplasia ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

scholarly journals Congenital Lipoid Adrenal Hyperplasia Caused by a Novel Splicing Mutation in the Gene for the Steroidogenic Acute Regulatory Protein

2004 ◽  
Vol 89 (2) ◽  
pp. 946-951 ◽  
Author(s):  
Alexis A. González ◽  
M. Loreto Reyes ◽  
Cristian A. Carvajal ◽  
Jaime A. Tobar ◽  
Lorena M. Mosso ◽  
...  
Keyword(s):  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Wild Type ◽  
Adrenal Hyperplasia ◽  
Cos Cells ◽  
Star Protein ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Intron 1 ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

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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