The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Lourdes Ibáñez - One of the best experts on this subject based on the ideXlab platform.
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IGF2/H19 hypomethylation in a patient with very low birthweight, preocious Pubarche and insulin resistance
BMC Medical Genetics, 2012Co-Authors: Rinki Murphy, Lourdes Ibáñez, Andrew T. Hattersley, Jörg TostAbstract:Background Insulin like growth factor 2 ( IGF2 ) is an imprinted gene, which has an important role in fetal growth as established in mice models. IGF2 is downregulated through hypomethylation of a differentially methylated region (DMR) in Silver Russell syndrome (SRS), characterised by growth restriction. We have previously reported that severe pre- and post-natal growth restriction associated with insulin resistance and precocious Pubarche in a woman without body asymmetry or other SRS features resulted from a balanced translocation affecting the regulation of her IGF2 gene expression. We hypothesised that severe pre- and post-natal growth restriction associated with insulin resistance and precocious Pubarche in the absence of SRS are also caused by downregulation of IGF2 through hypomethylation, gene mutation or structural chromosomal abnormalities. Methods We performed routine karyotyping, IGF2 gene sequencing and investigated DNA methylation of the IGF2 differentially methylated region (DMR)0 and H19 DMR using pyrosequencing, in four women selected for very low birth weight (
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igf2 h19 hypomethylation in a patient with very low birthweight preocious Pubarche and insulin resistance
BMC Medical Genetics, 2012Co-Authors: Rinki Murphy, Lourdes Ibáñez, Andrew T. Hattersley, Jörg TostAbstract:Background Insulin like growth factor 2 (IGF2) is an imprinted gene, which has an important role in fetal growth as established in mice models. IGF2 is downregulated through hypomethylation of a differentially methylated region (DMR) in Silver Russell syndrome (SRS), characterised by growth restriction. We have previously reported that severe pre- and post-natal growth restriction associated with insulin resistance and precocious Pubarche in a woman without body asymmetry or other SRS features resulted from a balanced translocation affecting the regulation of her IGF2 gene expression. We hypothesised that severe pre- and post-natal growth restriction associated with insulin resistance and precocious Pubarche in the absence of SRS are also caused by downregulation of IGF2 through hypomethylation, gene mutation or structural chromosomal abnormalities.
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IGF2/H19 hypomethylation in a patient with very low birthweight, preocious Pubarche and insulin resistance
BMC medical genetics, 2012Co-Authors: Rinki Murphy, Lourdes Ibáñez, Andrew T. Hattersley, Jörg TostAbstract:Background Insulin like growth factor 2 (IGF2) is an imprinted gene, which has an important role in fetal growth as established in mice models. IGF2 is downregulated through hypomethylation of a differentially methylated region (DMR) in Silver Russell syndrome (SRS), characterised by growth restriction. We have previously reported that severe pre- and post-natal growth restriction associated with insulin resistance and precocious Pubarche in a woman without body asymmetry or other SRS features resulted from a balanced translocation affecting the regulation of her IGF2 gene expression. We hypothesised that severe pre- and post-natal growth restriction associated with insulin resistance and precocious Pubarche in the absence of SRS are also caused by downregulation of IGF2 through hypomethylation, gene mutation or structural chromosomal abnormalities.
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clinical spectrum of premature Pubarche links to metabolic syndrome and ovarian hyperandrogenism
Reviews in Endocrine & Metabolic Disorders, 2009Co-Authors: Lourdes Ibáñez, Ruben Diaz, Abel Lopezbermejo, Maria Victoria MarcosAbstract:Premature Pubarche—defined as the appearance of pubic hair before age 8 years in girls and 9 years in boys—has been traditionally considered a benign entity. However, recent evidence supports the notion that premature Pubarche in girls may be a forerunner of the metabolic syndrome, and may precede the development of clinical ovarian androgen excess in adolescence. This sequence seems to occur more frequently when premature Pubarche was preceded by reduced fetal growth and followed by excessive postnatal catch-up in height and particularly in weight; hyperinsulinemia appears to be a key factor in the development of this sequence of events. In girls with premature Pubarche and a history of a low birth weight, puberty tends to start earlier and to have a faster course, so that final height may be moderately reduced. In these girls, metformin therapy may reverse the progression to clinical ovarian hyperandrogenism, normalize body composition and excess visceral fat, and delay pubertal progression without attenuating linear growth and bone mineralization, suggesting that adult height may be improved. Long-term follow-up of these patients is needed to fully determine the ultimate effects of insulin sensitization as well as the maintenance of these benefits after discontinuation of therapy.
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Insulin Gene Variable Number of Tandem Repeat Genotype and the Low Birth Weight, Precocious Pubarche, and Hyperinsulinism Sequence
The Journal of clinical endocrinology and metabolism, 2001Co-Authors: Lourdes Ibáñez, Maria Victoria Marcos, Neus Potau, Francis De Zegher, Ken K Ong, David B DungerAbstract:Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious Pubarche (pubic hair
Neus Potau - One of the best experts on this subject based on the ideXlab platform.
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Insulin Gene Variable Number of Tandem Repeat Genotype and the Low Birth Weight, Precocious Pubarche, and Hyperinsulinism Sequence
The Journal of clinical endocrinology and metabolism, 2001Co-Authors: Lourdes Ibáñez, Maria Victoria Marcos, Neus Potau, Francis De Zegher, Ken K Ong, David B DungerAbstract:Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious Pubarche (pubic hair
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insulin gene variable number of tandem repeat genotype and the low birth weight precocious Pubarche and hyperinsulinism sequence
The Journal of Clinical Endocrinology and Metabolism, 2001Co-Authors: Lourdes Ibáñez, Maria Victoria Marcos, Neus Potau, Francis De Zegher, Ken K Ong, David B DungerAbstract:Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious Pubarche (pubic hair <8 yr). We hypothesized that these associations might be influenced by the insulin gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with precocious Pubarche, hyperinsulinemia was assessed from mean insulin levels during an oral glucose load (MSI), and insulin sensitivity was determined from fasting glucose and insulin levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in precocious Pubarche girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in precocious Pubarche and control girls. However among precocious Pubarche girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III ge...
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sensitization to insulin in adolescent girls to normalize hirsutism hyperandrogenism oligomenorrhea dyslipidemia and hyperinsulinism after precocious Pubarche
The Journal of Clinical Endocrinology and Metabolism, 2000Co-Authors: Lourdes Ibáñez, Maria Victoria Marcos, Carme Valls, Neus Potau, Francis De ZegherAbstract:Precocious Pubarche in girls is often preceded by low weight at birth and followed by hirsutism, ovarian hyperandrogenism, and oligomenorrhea in adolescence, the latter usually being accompanied by dyslipidemia and hyperinsulinism, which are, in turn, two major risk factors for cardiovascular disease in later life. We hypothesized that insulin resistance may be a key pathogenetic factor in this sequence. We tested the hypothesis by assessing the effects of an insulin-sensitizing agent, metformin, given at a daily dose of 1275 mg for 6 months to 10 nonobese adolescent girls (mean age, 16.8 yr; body mass index, 21.9 kg/m2; birth weight, 2.7 kg) with hirsutism, ovarian hyperandrogenism (diagnosis by GnRH agonist test), oligomenorrhea, dyslipidemia, and hyperinsulinemia after precocious Pubarche. Before the metformin trial, longitudinal studies in these girls had shown that hyperinsulinism was present at prepubertal diagnosis of precocious Pubarche, and that it increased markedly in late puberty or early post...
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Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious Pubarche.
Journal of Clinical Endocrinology & Metabolism, 2000Co-Authors: Lourdes Ibáñez, Maria Victoria Marcos, Carme Valls, Neus Potau, Francis De ZegherAbstract:Precocious Pubarche in girls is often preceded by low weight at birth and followed by hirsutism, ovarian hyperandrogenism, and oligomenorrhea in adolescence, the latter usually being accompanied by dyslipidemia and hyperinsulinism, which are, in turn, two major risk factors for cardiovascular disease in later life. We hypothesized that insulin resistance may be a key pathogenetic factor in this sequence. We tested the hypothesis by assessing the effects of an insulin-sensitizing agent, metformin, given at a daily dose of 1275 mg for 6 months to 10 nonobese adolescent girls (mean age, 16.8 yr; body mass index, 21.9 kg/m2; birth weight, 2.7 kg) with hirsutism, ovarian hyperandrogenism (diagnosis by GnRH agonist test), oligomenorrhea, dyslipidemia, and hyperinsulinemia after precocious Pubarche. Before the metformin trial, longitudinal studies in these girls had shown that hyperinsulinism was present at prepubertal diagnosis of precocious Pubarche, and that it increased markedly in late puberty or early postmenarche. Metformin treatment was well tolerated and was accompanied by a marked drop in hirsutism score, insulin response to oral glucose tolerance test, free androgen index, and baseline testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate levels (all P < 0.01). During metformin treatment, the LH and 17-hydroxyprogesterone hyperresponses to GnRH agonist were attenuated (P < 0.01); serum triglyceride, total cholesterol, and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol rose. All girls reported regular menses within 4 months. Withdrawal of metformin treatment was followed, within 3 months, by a consistent reversal toward pretreatment conditions. In conclusion, metformin treatment reduced hyperinsulinemia, hirsutism, and hyperandrogenism; attenuated the LH and 17-hydroxyprogesterone hyperresponses to GnRH agonist; improved the atherogenic lipid profile; and restored eumenorrhea in nonobese adolescent girls with a history of precocious Pubarche. These observations corroborate the idea that insulin resistance may indeed be a prime factor underpinning the sequence from reduced fetal growth, through precocious Pubarche, to adolescent endocrinopathies that are reminiscent of so-called polycystic ovary syndrome.
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Precocious Pubarche in girls and the development of androgen excess.
Journal of pediatric endocrinology & metabolism : JPEM, 2000Co-Authors: Lourdes Ibáñez, Neus Potau, David B Dunger, De Zegher FAbstract:The prevalence of ovarian hyperandrogenism, hyperinsulinism and dyslipidemia is increased among adolescent girls with a history of premature Pubarche (defined as the appearance of pubic hair before the age of 8 yr). The ovarian hyperandrogenism is characterized by clinical signs of androgen excess and by an exaggerated ovarian 17-hydroxyprogesterone response to GnRH agonist stimulation. The hyperinsulinism and dyslipidemia are detectable before and during pubertal development, and are commonly accompanied by low serum levels of insulin-like growth factor binding-protein 1 (IGFBP-1) and sex hormone-binding globulin (SHBG), and by an increased prevalence of anovulation from late adolescence onwards, even in the absence of clinical signs of androgen excess. In girls, premature Pubarche, hyperinsulinism, low IGFBP-1, dyslipidemia, anovulation and hyperandrogenism--and some combinations of these--have been related to reduced fetal growth, indicating that these constellations or sequences may have a prenatal origin. Together, these findings suggest that premature Pubarche in girls should no longer be merely regarded as a normal variant of development, but rather as a childhood marker pointing to an increased risk for a polyendocrine-metabolic disorder of prenatal origin.
Berenice B. Mendonca - One of the best experts on this subject based on the ideXlab platform.
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Premature Pubarche due to Exogenous Testosterone Gel or Intense Diaper Rash Prevention Cream Use: A Case Series.
Hormone research in paediatrics, 2019Co-Authors: Carolina Ramos, Ana Claudia Latronico, Delanie B. Macedo, Tania A. S. S. Bachega, Marilza Leal Nascimento, Guiomar Madureira, Vinicius Nahime Brito, Berenice B. MendoncaAbstract:Background/Aims: Premature Pubarche is associated with conditions such as virilizing congenital adrenal hyperplasia, androgen-secreting tumors, and exogenous exposure to androgen products. We describe the clinical and hormonal features of a series of children who were referred to endocrine evaluation due to premature Pubarche. Methods: This is a retrospective case series study of 14 children with premature Pubarche and/or virilization. Five were unintentionally exposed to testosterone gel (parental use). Nine patients were intensely exposed to diaper rash prevention creams. Clinical and laboratory data were revised. Results: Moderate to severe virilization was detected in the 5 patients (2 boys and 3 girls) who were exposed to testosterone gel. These patients had pubic hair development associated with clitoromegaly (3/3), penile enlargement (2/2), and accelerated growth (5/5). Testosterone levels were elevated in 4/5 patients associated with normal prepubertal gonadotropin levels and adrenal androgen precursors. The 9 children who were intensely exposed to diaper rash prevention creams had mild Pubarche (intermediate hair) without any other clinical manifestation of pubertal development. Three of them exhibited pubic hair thinning after cream withdrawal. Conclusion: Unintentional topical androgen exposure or the intense use of diaper rash prevention cream should be ruled out in children with precocious Pubarche and/or virilization signs to avoid misdiagnosis and expendable investigation.
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Mutations in the type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature Pubarche in girls
Clinical endocrinology, 2000Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:OBJECTIVE Most previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature Pubarche and a hormonal diagnosis of 3β-hydroxysteroid dehydrogenase deficiency. DESIGN From 30 girls with premature Pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS Premature Pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.
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mutations in the type ii 3β hydroxysteroid dehydrogenase hsd3b2 gene can cause premature Pubarche in girls
Clinical Endocrinology, 2000Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:OBJECTIVE Most previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature Pubarche and a hormonal diagnosis of 3β-hydroxysteroid dehydrogenase deficiency. DESIGN From 30 girls with premature Pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS Premature Pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.
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mutations in the type ii 3 beta hydroxysteroide dehydrogenase gene 3 beta hsd in girls with premature Pubarche
Pediatric Research, 1999Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:Mutations in the Type II 3β-Hydroxysteroide Dehydrogenase Gene (3β-HSD) in Girls with Premature Pubarche
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Mutations in the Type II 3|[beta]|-Hydroxysteroide Dehydrogenase Gene (3|[beta]|-HSD) in Girls with Premature Pubarche
Pediatric Research, 1999Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:Mutations in the Type II 3β-Hydroxysteroide Dehydrogenase Gene (3β-HSD) in Girls with Premature Pubarche
Ivo J. P. Arnhold - One of the best experts on this subject based on the ideXlab platform.
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Mutations in the type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature Pubarche in girls
Clinical endocrinology, 2000Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:OBJECTIVE Most previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature Pubarche and a hormonal diagnosis of 3β-hydroxysteroid dehydrogenase deficiency. DESIGN From 30 girls with premature Pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS Premature Pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.
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mutations in the type ii 3β hydroxysteroid dehydrogenase hsd3b2 gene can cause premature Pubarche in girls
Clinical Endocrinology, 2000Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:OBJECTIVE Most previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature Pubarche and a hormonal diagnosis of 3β-hydroxysteroid dehydrogenase deficiency. DESIGN From 30 girls with premature Pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS Premature Pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.
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mutations in the type ii 3 beta hydroxysteroide dehydrogenase gene 3 beta hsd in girls with premature Pubarche
Pediatric Research, 1999Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:Mutations in the Type II 3β-Hydroxysteroide Dehydrogenase Gene (3β-HSD) in Girls with Premature Pubarche
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Mutations in the Type II 3|[beta]|-Hydroxysteroide Dehydrogenase Gene (3|[beta]|-HSD) in Girls with Premature Pubarche
Pediatric Research, 1999Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:Mutations in the Type II 3β-Hydroxysteroide Dehydrogenase Gene (3β-HSD) in Girls with Premature Pubarche
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mutation in 3s hydroxysteroid dehydrogenase type ii associated with pseudohermaphroditism in males and premature Pubarche or cryptic expression in females
Journal of Molecular Endocrinology, 1994Co-Authors: Berenice B. Mendonca, Ivo J. P. Arnhold, Alan J Russell, M Vasconcelosleite, W Bloise, B L Wajchenberg, W Nicolau, R G Sutcliffe, A M WallaceAbstract:A mutation (A82T) is described in the coding sequence of the gene for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type II that is associated with variable clinical consequences. Four homozygotes are described, all of which showed elevated levels of delta 5 steroids consistent with 3 beta-HSD deficiency. Two males from a consanguineous family were found to be homozygous for A82T and were affected with pseudohermaphroditism. They differed in their degree of mild salt loss. In the same family a female was found to be homozygous for A82T, but was clinically normal and had no history of premature Pubarche or of abnormal menstrual cycles. However, in an apparently unrelated family, the A82T mutation was found in a female affected with premature Pubarche. This is the first report of a proven mutation in 3 beta-HSD type II associated with premature Pubarche.
Suemi Marui - One of the best experts on this subject based on the ideXlab platform.
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Mutations in the type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature Pubarche in girls
Clinical endocrinology, 2000Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:OBJECTIVE Most previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature Pubarche and a hormonal diagnosis of 3β-hydroxysteroid dehydrogenase deficiency. DESIGN From 30 girls with premature Pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS Premature Pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.
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mutations in the type ii 3β hydroxysteroid dehydrogenase hsd3b2 gene can cause premature Pubarche in girls
Clinical Endocrinology, 2000Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:OBJECTIVE Most previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature Pubarche and a hormonal diagnosis of 3β-hydroxysteroid dehydrogenase deficiency. DESIGN From 30 girls with premature Pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS Premature Pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.
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mutations in the type ii 3 beta hydroxysteroide dehydrogenase gene 3 beta hsd in girls with premature Pubarche
Pediatric Research, 1999Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:Mutations in the Type II 3β-Hydroxysteroide Dehydrogenase Gene (3β-HSD) in Girls with Premature Pubarche
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Mutations in the Type II 3|[beta]|-Hydroxysteroide Dehydrogenase Gene (3|[beta]|-HSD) in Girls with Premature Pubarche
Pediatric Research, 1999Co-Authors: Suemi Marui, Ivo J. P. Arnhold, Margaret De Castro, Ana Claudia Latronico, Lucila Leico Kagohara Elias, Ayrton Custódio Moreira, Berenice B. MendoncaAbstract:Mutations in the Type II 3β-Hydroxysteroide Dehydrogenase Gene (3β-HSD) in Girls with Premature Pubarche