The Experts below are selected from a list of 2124 Experts worldwide ranked by ideXlab platform
Amit V Pandey - One of the best experts on this subject based on the ideXlab platform.
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inhibition of placental cyp19a1 activity remains as a valid hypothesis for 46 xx Virilization in p450 oxidoreductase deficiency
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Christa E Fluck, Amit V Pandey, Shaheena Parween, Maria Natalia Rojas VelazquezAbstract:Cytochrome P450 oxidoreductase deficiency (PORD), caused by mutations in P450 oxidoreductase (POR), is a disorder of steroid metabolism often characterized by disordered sexual development (1⇓–3). POR is required for enzymatic activities of multiple cytochrome P450 enzymes (4). In PNAS, Reisch et al. (5) propose “alternative pathway androgen biosynthesis” as the cause of 46,XX Virilization in PORD. We are pleased to see the expansion of the role of alternative pathway in sexual development previously demonstrated by us in 46,XY individuals (6), but have some concerns regarding the assumption that Virilization of 46,XX individuals in PORD is mainly via an alternative pathway. The choice of steroid analysis by Reisch et al. (5) from only 46,XY individuals to propose a hypothesis for 46,XX Virilization is baffling. Another recent study found low to undetectable levels of 17-hydroxy-dihydroprogesterone, 17-hydroxy-allopregnanolone, and androsterone, the steroids in alternative pathway produced via CYP17A1, in the 46,XX fetal adrenals and attributed it to a lack of SRD5A1 expression in fetal adrenal (7). We have previously reported that … [↵][1]1To whom correspondence may be addressed. Email: amit{at}pandeylab.org. [1]: #xref-corresp-1-1
Toshiaki Tanaka - One of the best experts on this subject based on the ideXlab platform.
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cytochrome p450 oxidoreductase gene mutations and antley bixler syndrome with abnormal genitalia and or impaired steroidogenesis molecular and clinical studies in 10 patients
The Journal of Clinical Endocrinology and Metabolism, 2005Co-Authors: Maki Fukami, Reiko Horikawa, Toshiaki Tanaka, Toshiro Nagai, Yasuhiro Naiki, Naoko Sato, Torayuki Okuyama, Hideo Nakai, Shun Soneda, Katsuhiko TachibanaAbstract:We report on molecular and clinical findings in 10 Japanese patients (four males and six females) from eight families (two pairs of siblings and six isolated cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or impaired steroidogenesis. Direct sequencing was performed for all the 15 exons of cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H and Y578C), a 24-bp deletion mutation resulting in loss of nine amino acids and creation of one amino acid (L612_W620delinsR), a single bp insertion mutation leading to frameshift (I444fsX449), and a silent mutation (G5G). R457H has previously been shown to be a pathologic mutation, and computerized modeling analyses indicated that the 15A>G for G5G could disturb an exonic splicing enhancer motif, and the remaining three mutations should affect protein conformations. Six patients were compound heterozygotes, and three patients were R457H homozygotes; no mutation was identified on one allele of the remaining one patient. Clinical findings included various degrees of skeletal features, such as brachycephaly, radiohumeral synostosis, and digital joint contractures in patients of both sexes, normal-to-poor masculinization during fetal and pubertal periods in male patients, Virilization during fetal life and poor pubertal development without worsening of Virilization in female patients, and relatively large height gain and delayed bone age from the pubertal period in patients of both sexes, together with maternal Virilization during pregnancy. Blood cholesterol was grossly normal, and endocrine studies revealed defective CYP17A1 and CYP21A2 activities. The results suggest that Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis is caused by POR mutations, and that clinical features are variable and primarily explained by impaired activities of POR-dependent CYP51A1, CYP17A1, CYP21A2, and CYP19A1.
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a case of female pseudohermaphroditism caused by aromatase deficiency
Clinical Pediatric Endocrinology, 2004Co-Authors: Keisuke Nagasaki, Kazuo Fujisawa, Reiko Horikawa, Ikue Hata, Yosuke Shigematsu, Toshiaki TanakaAbstract:Female pseudohermaphroditism is caused by several etiologies. Here we report a case of aromatase deficiency who showed ambiguous genitalia and maternal Virilization during pregnancy. The mother had noticed her own Virilization from 16 wk of gestation without androgen exposure and had low urinary estriol levels (5~10 μg/ml at 35 wk of gestation). At birth, the patient presented severe Virilization (Prader V), and was assigned as a male with a micropenis and unpalpable testes but the patient had a normal female karyotype and a uterus and cystic ovaries found by magnetic resonance imaging. The patient had a increase in serum 17α-hydroxy progesterone levels (basal 4.9 → 37 ng/ml after a single 0.25 mg/m2 infusion of ACTH), but the increase in adrenal androgen was not sufficient to virilize the external genitalia. Dehydroepiandrosterone, 17α-hydroxy pregnenolone and deoxycorticosterone were within the normal ranges. These findings suggested a diagnosis of nonadrenal female pseudohermaphroditism. From the clinical features and biochemical data, we endocrinologically diagnosed her as having an aromatase deficiency. The aromatase gene is now under investigation for definite diagnosis. We finally agreed that aromatase deficiency should be suspected when both the mother and the newborn have been virilized.
Christa E Fluck - One of the best experts on this subject based on the ideXlab platform.
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inhibition of placental cyp19a1 activity remains as a valid hypothesis for 46 xx Virilization in p450 oxidoreductase deficiency
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Christa E Fluck, Amit V Pandey, Shaheena Parween, Maria Natalia Rojas VelazquezAbstract:Cytochrome P450 oxidoreductase deficiency (PORD), caused by mutations in P450 oxidoreductase (POR), is a disorder of steroid metabolism often characterized by disordered sexual development (1⇓–3). POR is required for enzymatic activities of multiple cytochrome P450 enzymes (4). In PNAS, Reisch et al. (5) propose “alternative pathway androgen biosynthesis” as the cause of 46,XX Virilization in PORD. We are pleased to see the expansion of the role of alternative pathway in sexual development previously demonstrated by us in 46,XY individuals (6), but have some concerns regarding the assumption that Virilization of 46,XX individuals in PORD is mainly via an alternative pathway. The choice of steroid analysis by Reisch et al. (5) from only 46,XY individuals to propose a hypothesis for 46,XX Virilization is baffling. Another recent study found low to undetectable levels of 17-hydroxy-dihydroprogesterone, 17-hydroxy-allopregnanolone, and androsterone, the steroids in alternative pathway produced via CYP17A1, in the 46,XX fetal adrenals and attributed it to a lack of SRD5A1 expression in fetal adrenal (7). We have previously reported that … [↵][1]1To whom correspondence may be addressed. Email: amit{at}pandeylab.org. [1]: #xref-corresp-1-1
Tania A S S Bachega - One of the best experts on this subject based on the ideXlab platform.
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the effect of fetal androgen metabolism related gene variants on external genitalia Virilization in congenital adrenal hyperplasia
Clinical Genetics, 2013Co-Authors: Laura C Kaupert, Berenice B. Mendonca, Sofia Helena Valente De Lemosmarini, M P De Mello, Ricardo P P Moreira, Vinicius Nahime Brito, Alexander A L Jorge, Carlos Alberto Longui, Gil Guerra, Tania A S S BachegaAbstract:The 21-hydroxylase deficiency (21OHD) is caused by CYP21A2 mutations resulting in severe or moderate enzymatic impairments. 21OHD females carrying similar genotypes present different degrees of external genitalia Virilization, suggesting the influence of other genetic factors. Single nucleotide variants (SNVs) in the CYP3A7 gene and in its transcription factors, related to fetal 19-carbon steroid metabolism, could modulate the genital phenotype. To evaluate the influence of the 21OHD genotypes and the CYP3A7, PXR and CAR SNVs on the genital phenotype in 21OHD females. Prader scores were evaluated in 183 patients. The CYP3A7, PXR and CAR SNVs were screened and the 21OHD genotypes were classified according to their severity: severe and moderate groups. Patients with severe genotype showed higher degree of genital Virilization (Prader median III, IQR III-IV) than those with moderate genotype (III, IQR II-III) (p < 0.001). However, a great overlap was observed between genotype groups. Among all the SNVs tested, only the CAR rs2307424 variant correlated with Prader scores (r(2) = 0.253; p = 0.023). The CYP21A2 genotypes influence the severity of genital Virilization in 21OHD females. We also suggest that the CAR variant, which results in a poor metabolizer phenotype, could account for a higher degree of external genitalia Virilization.
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the degree of external genitalia Virilization in girls with 21 hydroxylase deficiency appears to be influenced by the cag repeats in the androgen receptor gene
Clinical Endocrinology, 2007Co-Authors: Rosana O Rocha, Berenice B. Mendonca, Carlos Alberto Longui, Ana Elisa C Billerbeck, Emilia M Pinto, Karla F S Melo, Chin Jia Lin, Tania A S S BachegaAbstract:Summary Background Women with 21-hydroxylase deficiency present much variability in external genitalia Virilization, even among those with similar impairments of 21-hydroxylase (21OH) activity. Objective To evaluate if the number of CAG (nCAG) repeats of the androgen receptor gene influences the degree of external genitalia Virilization in women with CYP21A2 mutations, grouped according to impairment of 21OH activity. Patients The nCAG was determined in 106 congenital adrenal hyperplasia (CAH) patients and in 302 controls. The patients were divided, according to their CYP21A2 genotypes, into Groups A and B, which confer total and severe impairment of 21OH activity, respectively. Methods The inactivation pattern of the X-chromosome was studied through genomic DNA digestion with Hpa II. The CAG repeat region was amplified by polymerase chain reaction (PCR) and analysed by GeneScan. Results The nCAG and the frequency of severe skewed X-inactivation did not differ between normal women and patients. The nCAG median in genotype A was 20·7 (IQR 2·3) for Prader I + II, 22·5 (3·6) for Prader III and 21 (2·9) for Prader IV + V (P 0·05). A significant difference was found regarding the nCAG median in patients presenting Prader III from genotypes A and B. Conclusions We observed great variability in the degree of external genitalia Virilization in both CYP21A2 genotypes, and we showed that the CAG repeats of the androgen receptor gene influences this phenotypic variability.
Bente Sørensen - One of the best experts on this subject based on the ideXlab platform.
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sertoli leydig cell tumour of the ovary a rare cause of Virilization after menopause
Apmis, 1993Co-Authors: Tine Plato Hansen, Bente SørensenAbstract:A case of Sertoli-Leydig cell tumour of the ovary causing Virilization in a postmenopausal woman is presented. The patient had increasing facial hair growth, deepening of the voice, a dull pain in the lower part of the abdomen and enlargement of the clitoris. Laboratory investigations showed an elevated level of plasma testosterone. Considering an ovarian tumour the most likely cause of the above-mentioned findings, hysterectomy with bilateral salpingo-oophorectomy was performed. Both ovaries were macroscopically normal at operation, but pathological examination revealed a small well-differentiated Sertoli-Leydig cell tumour in the left ovary. Follow-up 3 months later showed decreasing signs of Virilization and normalization of the hormone levels.
