ANDRESA DE SANTI RODRIGUES

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina

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Assunto: Endocrinology & Metabolism ×

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Agora exibindo 1 - 10 de 15
  • article 13 Citação(ões) na Scopus
    Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor
    (2018) BATISTA, Rafael Loch; RODRIGUES, Andresa De Santi; MACHADO, Aline Zamboni; NISHI, Mirian Yumie; CUNHA, Flavia Siqueira; SILVA, Rosana Barbosa; COSTA, Elaine M. F.; MENDONCA, Berenice B.; DOMENICE, Sorahia
    Background: Androgen insensitivity syndrome (AIS) is the most frequent etiology of 46, XY disorders of sex development (DSDs), and it is an X-linked disorder caused by mutations in the androgen receptor (AR) gene. AIS patients present a broad phenotypic spectrum and individuals with a partial phenotype present with different degrees of undervirilized external genitalia. There are more than 500 different AR gene allelic variants reported to be linked to AIS, but the presence of somatic mosaicisms has been rarely identified. In the presence of a wild-type AR gene, a significant degree of spontaneous virilization at puberty can be observed, and it could influence the gender assignment, genetic counseling and the clinical and psychological management of these patients and the psychosexual outcomes of these patients are not known. Case presentation: In this study, we report two patients with AR allelic variants in heterozygous (c.382G>T and c.1769-1G>C) causing a partial AIS (PAIS) phenotype. The first patient was raised as female and she had undergone a gonadectomy at puberty. In both patients there was congruency between gender of rearing and gender identity and gender role. Conclusions: Somatic mosaicism is rare in AIS and nonsense AR variant allelic can cause partial AIS phenotype in this situation. Despite the risk of virilization and prenatal androgen exposure, the gender identity and gender role was concordant with sex of rearing in both cases. A better testosterone response can be expected in male individuals and this should be considered in the clinical management.
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    Molecular Confirmatory Test Improves the Accuracy of Congenital Adrenal Hyperplasia Diagnosis in Newborn Screening Program
    (2016) MIRANDA, Mirela; SANTOS, Eliane dos; CARVALHO, Daniel de; RODRIGUES, Andressa; NADER, Ivana; AMELIO JUNIOR, Joao; MENDONCA, Berenice; BACHEGA, Tania
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    Gonadal Tumor Risk, Bone Mineral Density, and Genetics, Clinical, Hormonal, and Psychosexual Aspects of a Large Androgen Insensitivity Syndrome Cohort
    (2021) BATISTA, Rafael Loch; RAMOS, Raquel Martinez; NISHI, Miriam; DALLAGO, Renata; ELIAS, Felipe; RODRIGUES, Andresa di Santi; DOMENICE, Sorahia; MENDONCA, Berenice B.
  • article 2 Citação(ões) na Scopus
    High frequency of non-classical congenital adrenal hyperplasia form among children with persistently elevated levels of 17-hydroxyprogesterone after newborn screening
    (2019) CASTRO, Patricia S.; RASSI, Tatiana O.; ARAUJO, Raquel F.; PEZZUTI, Isabela L.; RODRIGUES, Andresa S.; BACHEGA, Tania A. S. S.; SILVA, Ivani N.
    Background: Early diagnosis after newborn screening (NBS) for congenital adrenal hyperplasia (CAH) allows proper treatment, reducing mortality rates and preventing development of hyperandrogenic manifestations and incorrect sex assignment at birth. Despite the high NBS sensitivity to detect CAH classical forms, one of the main issues is identifying asymptomatic children who remained with increased 17-hydroxyprogesterone (17-OHP) levels. In this study, we aimed to contribute to understanding the diagnosis of these children. Methods: Children with increased serum 17-OHP levels, and without disease-related clinical features during follow-up, underwent the entire CYP21A2 gene sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis (SALSA MLPA P050B CAH). Patients' genotypes were subsequently sorted as compatible with CAH disease, and children were evaluated to determine the clinical status. Results: During the study period, 106,476 newborns underwent CAH NBS. During follow-up, 328 children (0.3%) were identified as having false-positive tests and 295 were discharged after presenting with 17-OHP levels within reference values. Thirty-three remained asymptomatic and with increased serum 17-OHP levels after a mean follow-up of 3.4 years, and were subjected to molecular analysis. Seventeen out of the 33 children carried mutations: seven in the heterozygous state, nine carried non-classical genotypes and the remaining child carried a classical genotype. Conclusions: We found a high frequency of non-classical CAH (NCCAH) diagnosis among children with persistent elevation of 17-OHP levels. Our findings support molecular study as decisive for elucidating diagnosis in these asymptomatic children. Molecular analysis as a confirmatory test is relevant to guide their follow-up, allows genetic counseling and avoids over treating NCCAH form.
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    Twenty Years Experience in Congenital Adrenal Hyperplasia: Clinical, Hormonal and Molecular Characteristics in a Large Cohort
    (2015) MIRANDA, M.; CARVALHO, D.; GOMES, L.; MADUREIRA, G.; RODRIGUES, A.; MENDONCA, B.; BACHEGA, T.
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    Isolated Growth Hormone Deficiency with Advanced Bone Age: Phenotypic Interaction between GHRH Receptor and CYP21A2 Mutations Diagnosed by Sanger and Whole Exome Sequencing
    (2016) CORREA, F. A.; FRANCA, M. M.; FANG, Q.; MA, Q.; OZEL, B. A.; BACHEGA, T. A.; RODRIGUES, A.; LI, J. Z.; MENDONCA, B. B.; JORGE, A. A. L.; CARVALHO, L. R.; CAMPER, S. A.; ARNHOLD, I. J. P.
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    Exonic Splicing Mutations by Silent Nucleotide Variation in the Androgen Receptor Gene Causes Androgen Insensitivity Syndrome
    (2016) BATISTA, Rafael Loch; RODRIGUES, Andreza de Santi; SILVA, Tathiana Evilen da; CUNHA, Flavia Siqueira; GOMES, Nathalia Lisboa; RODRIGUES, Daniela; DOMENICE, Sorahia; COSTA, Elaine Frade; MENDONCA, Berenice Bilharinho de
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    The pre- and postnatal influence of androgens in the psychosexual development of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency
    (2023) BATISTA, Rafael Loch; INACIO, Marlene; MADUREIRA, Guiomar; MIRANDA, Mirela; GOMES, Larissa; RODRIGUES, Andresa; FUNARI, Mariana; BACHEGA, Tania; MENDONCA, Berenice Bilharinho
  • article 5 Citação(ões) na Scopus
    Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing
    (2017) CORREA, Fernanda A.; FRANCA, Marcela M.; FANG, Qing; MA, Qianyi; BACHEGA, Tania A.; RODRIGUES, Andresa; OZEL, Bilge A.; LI, Jun Z.; MENDONCA, Berenice B.; JORGE, Alexander A. L.; CARVALHO, Luciani R.; CAMPER, Sally A.; ARNHOLD, Ivo J. P.
    Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS -3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.
  • article 12 Citação(ões) na Scopus
    Mobile DNA in Endocrinology: LINE-1 Retrotransposon Causing Partial Androgen Insensitivity Syndrome
    (2019) BATISTA, Rafael Loch; YAMAGUCHI, Katsumi; RODRIGUES, Andresa di Santi; NISHI, Mirian Yumie; GOODIER, John L.; CARVALHO, Luciani Renata; DOMENICE, Sorahia; COSTA, Elaine M. F.; KAZAZIAN JR., Haig H.; MENDONCA, Berenice Bilharinho
    Context: Androgen insensitivity syndrome (AIS) is the most common cause of disorders of sex development in 46,XY individuals. It is an X-linked condition usually caused by pathogenic allelic variants in the androgen receptor (AR) gene. The phenotype depends on the AR variant, ranging from severe undervirilization (complete AIS) to several degrees of external genitalia undervirilization. Although 90% of those with complete AIS will have AR mutations, this will only be true for 40% of those with partial AIS (PAIS). Objective: To identify the genetic etiology of AIS in a large multigenerational family with the PAIS phenotype. Participants: Nine affected individuals with clinical and laboratory findings consistent with PAIS and a normal exonic AR sequencing Settings: Endocrine clinic and genetic institute from two academic referral centers Design: Analysis of whole exons of the AR gene, including splicing regions, was performed, followed by sequencing of the 5'untranslated region (UTR) of the AR gene. Detailed phenotyping was performed at the initial diagnosis and long-term follow-up, and circulating levels of steroid gonadal hormones were measured in all affected individuals. AR expression was measured using RT-PCR and cultured fibroblasts. Results: All 46,XY family members with PAIS had inherited, in hemizygosity, a complex defect (similar to 1100 bp) in the 5'UTR region of the AR surrounded by a duplicated 18-bp sequence (target site duplication). This sequence is 99.7% similar to an active, long, interspersed element present on the X chromosome (AC002980; Xq22.2), which was inserted in the 5' UTR of the AR gene, severely reducing AR expression and leading to PAIS. Conclusion: The molecular diagnosis of PAIS remains challenging. The genomic effect of retrotransposon mobilization should be considered a possible molecular cause of AIS and other AR diseases.