Expression studies familial bilateral macronodular adrenal hyperplasia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171558 | GEO | 2021/04/07
REPOSITORIES: GEO
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Project description:Expression studies familial bilateral macronodular adrenal hyperplasia
| PRJNA720089 | ENA
Project description:To investigate Armadillo repeat-containing 5 (ARMC5) mutations in Chinese patients with familial and sporadic primary bilateral macronodular adrenal hyperplasia (PBMAH), we performed clinical data collection and ARMC5 sequencing for three PBMAH families and 23 sporadic PBMAH patients. ARMC5 pathogenic germline mutations were identified in all 3 PBMAH families. Secondary ARMC5 somatic mutations were found in two adrenal nodules from two PBMAH family members with ARMC5 germline mutations. PBMAH family members with ARMC5 pathogenic germline mutations displayed various clinical manifestations. ARMC5 pathogenic germline mutations were identified in 5 sporadic PBMAH patients among whom one patient displayed both hypercortisolism and primary aldosteronism. We detected a total of 10 ARMC5 pathogenic mutations, of which 8 had not been previously reported. Our results suggest that ARMC5 pathogenic germline mutations are common in familial and sporadic Chinese PBMAH patients, and demonstrate the importance of ARMC5 screening in PBMAH family members to detect patients with insidious PBMAH.
| S-EPMC5784932 | biostudies-literature
Project description:AIMAH is an ACTH-independent bilateral enlargement of the adrenal cortex occuring during adulthood. The enlargment is related to the growth of multiple benign nodules. This condition is associated with various degrees of cortisol hypersecretion. The occurence of several nodules in both adrenals, and the existence of familial forms, suggest the existence of a germline genetic predisposition. To find the gene(s), the aim of the project was to look for recurrent chromosomal alterations in the AIMAH nodules. Extensive mapping of somatic gains, losses and copy-neutral loss of heterozygosity (LOH) was performed with Affymetrix SNP6 arrays. A copy neutral LOH of 16p, occuring in 7 of 26 patients, was one of the only recurrent alterations, pointing towards a candidate gene in this region. Of note this condition differs from the congenital adrenal hyperplasias, related to genetic alterations of steroidogenesis (the latter is an ACTH dependent adrenal hyperplasia). Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples or peripheral blood samples. Copy number and LOH analysis of Affymetrix SNP6 arrays was performed for AIMAH nodules from 26 patients, including 18 with paired leucocyte and nodules (1 to 4 nodules per patient), and 8 with a single nodule (no paired leucocyte available)
2013-11-28 | E-GEOD-42171 | biostudies-arrayexpress
Project description:AIMAH is an ACTH-independent bilateral enlargement of the adrenal cortex occuring during adulthood. The enlargment is related to the growth of multiple benign nodules. This condition is associated with various degrees of cortisol hypersecretion. The occurence of several nodules in both adrenals, and the existence of familial forms, suggest the existence of a germline genetic predisposition. To find the gene(s), the aim of the project was to look for recurrent chromosomal alterations in the AIMAH nodules. Extensive mapping of somatic gains, losses and copy-neutral loss of heterozygosity (LOH) was performed with Affymetrix SNP6 arrays. A copy neutral LOH of 16p, occuring in 7 of 26 patients, was one of the only recurrent alterations, pointing towards a candidate gene in this region. Of note this condition differs from the congenital adrenal hyperplasias, related to genetic alterations of steroidogenesis (the latter is an ACTH dependent adrenal hyperplasia). Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples or peripheral blood samples.
2013-11-28 | GSE42171 | GEO
Project description:ContextFamilial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases.ObjectiveA locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified.DesignThe study design comprised single-nucleotide polymorphism genotyping and mutation detection.SettingThe study was conducted at secondary and tertiary referral centers.PatientsEighty probands from families referred for investigation of the genetic cause of FGD participated in the study.InterventionsThere were no interventions.ResultsAnalysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families.ConclusionsMutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD.
| S-EPMC2860769 | biostudies-literature
Project description:CONTEXT AND OBJECTIVES:Congenital adrenal hyperplasia (CAH) is one of the most prevalent, and potentially severe, genetic inborn errors of steroid synthesis directly affecting metabolism. Most patients are diagnosed and treated at an early age. There have been very limited reports of adults with CAH-associated adrenal myelolipomas. We aimed to analyze two families with CAH-associated giant adrenal myelolipomas caused by defects in CYP21A2 and CYP17A1 genes. PARTICIPANTS AND METHODS:A total of 14 individuals from two unrelated families were identified with either CYP21A2 or CYP17A1 mutations. Of note, 5 patients were found with adrenal myelolipomas. Total DNA isolated from the peripheral blood of the two probands was screened for potential mutations in the following susceptibility genes of CAH: CYP21A2, CYP11B1, CYP17A1, HSD17B3, HSD3B2, ARMC5, and STAR using Target Capture-Based Deep Sequencing; and Sanger sequencing was conducted for the family members to detect the potential mutations. RESULTS:In family 1, molecular genetics sequencing revealed a compound heterozygous mutation (c.293-13C>G / c.518T>A, p.I173N) in CYP12A2 in the patient and his brother. In family 2, all three female patients with adrenal myelolipomas were found to have a compound heterozygous mutation (c.1118A>T, p.H373L / c.1459_1467del9, p.D487_F489del) in CYP17A1. CONCLUSION:To avoid giant CAH-associated adrenal myelolipomas in adults, it is important to identify CAH early so appropriate treatment can be initiated to interrupt the chronic adrenal hyperstimulation resulting from increased ACTH. Genetic testing and counseling could be useful in CAH.
| S-EPMC6215793 | biostudies-other
Project description:ContextRadiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated.ObjectiveWe hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed.DesignA retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019.SettingTertiary care clinical research center.PatientsPatients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics.InterventionClinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota).Main outcome and measures17-hydroxycorticosteroids (17-OHS), ARMC5 genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume.ResultsA cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ± 11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76, P = 0.028), urinary free cortisol (R = 0.70, P = 0.035), and 17-OHS (R = 0.87, P = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in ARMC5 (R = 0.72, P = 0.018; R = 0.65, P = 0.042; and R = 0.73, P = 0.016, respectively).ConclusionsVolumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.
| S-EPMC7716656 | biostudies-literature
Project description:Rationale: Idiopathic interstitial pneumonia (IIP) and its’ familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in understanding the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown. Objectives: To evaluate gene expression in the lung tissue from patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) that were either familial or non-familial in origin and compare them to gene expression from normal lung parenchyma. Methods: We profiled RNA from lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal controls on a whole human genome oligonucleotide microarray. Results: Significant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. Keywords: disease state analysis
2006-10-01 | GSE5774 | GEO
Project description:OBJECTIVE:Corticotropin (ACTH)-independent hypercortisolism due to bilateral adrenocortical hyperplasia (BAH) in infancy is an extremely rare condition that is often caused by McCune Albright syndrome (MAS). MAS is caused by an activating mutation of the GNAS gene which leads to increased cyclic (c) adenosine monophosphate (AMP) signaling. Most forms of BAH are linked to increased cAMP signaling. We report the case of an infant with MAS who had BAH. METHODS:Genomic DNA fragments from blood and adrenal tissue encompassing regions (exons 8 and 9) with the hot spot activating missense GNAS mutations were amplified by classical bidirectional Sanger sequencing. RESULTS:The infant was found to carry the most common GNAS mutation, in exon 8 (c.602G >A, p. R201H), only in her adrenocortical tissue, despite extensive skin and other findings. CONCLUSIONS:We conclude that infants with MAS, despite absence of the GNAS activating mutation in blood, may still have significant clinical findings, including ACTH-independent hypercortisolism. Molecular confirmation of the diagnosis should be sought at the tissue level in these patients.
| S-EPMC6341467 | biostudies-literature
Project description:ContextBilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing's syndrome.ObjectiveThe aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma.Design and settingIn vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories.InterventionMutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies.Main outcome measureDetection of 17alpha-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes.ResultsHistological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17alpha-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway.ConclusionThis case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing's syndrome.
| S-EPMC2805485 | biostudies-literature