Browsing by Author "Baquedano, P"

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    Congenital lipoid adrenal hyperplasia caused by a novel splicing mutation in the gene for the steroidogenic acute regulatory protein
    (ENDOCRINE SOC, 2004) Gonzalez, AA; Reyes, ML; Carvajal, CA; Tobar, JA; Mosso, LM; Baquedano, P; Solar, A; Venegas, A; Fardella, CE
    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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    Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux - Results of a coordinated research project
    (SPRINGER, 2004) Orellana, P; Baquedano, P; Rangarajan, V; Zhao, JH; Eng, NDC; Fettich, J; Chaiwatanarat, T; Sonmezoglu, K; Kumar, D; Park, YH; Samuel, AM; Sixt, R; Bhatnagar, V; Padhy, AK
    Acute pyelonephritis (APN) may produce permanent renal damage (PRD), which can subsequently lead to diverse complications. We prospectively evaluated 147 females and 122 males (mean age 3.5 years) with APN in order to analyze the relationship between the presence of PRD, at the time of cortical renal scintigraphy, and age, gender, episodes of urinary tract infection (UTI), and presence of vesicoureteral reflux (VUR). There were 152 children studied after the first proven UTI. VUR was present in 150 children. PRD was observed in 170 children. There were no significant differences between boys and girls. PRD was found in 36.4% of children younger than I year and in 70.1% of those older than I year (P<0.0001). Of children with VUR, 72% had PRD compared with 52% of children without VUR (P<0.0001). Of children with a first episode of UTI, 55.9% developed PRD as did 72.6% of those with recurrent UTI (P=0.004). Our results showed that PRD in children with APN is important, especially in the presence of VUR, recurrent UTI, and older age.