A5062205784- Pituitary Gland Disorders and Treatments
- Adrenal and Paraganglionic Tumors
- Neuroendocrine Tumor Research Advances
- Growth Hormone and Insulin-like Growth Factors
- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Adrenal Hormones and Disorders
- Neurofibromatosis and Schwannoma Cases
- TGF-β signaling in diseases
- Hormonal Regulation and Hypertension
- Ubiquitin and proteasome pathways
- Cardiac tumors and thrombi
- Genetic factors in colorectal cancer
- Neuropeptides and Animal Physiology
- Retinoids in leukemia and cellular processes
- Animal Genetics and Reproduction
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Phosphodiesterase function and regulation
- Myasthenia Gravis and Thymoma
- Nuclear Structure and Function
- Chromatin Remodeling and Cancer
- Health Systems, Economic Evaluations, Quality of Life
- Renin-Angiotensin System Studies
Queen Mary University of London
2012-2025
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
2021-2025
Universidad Nacional Autónoma de México
2021-2025
Centro Medico Nacional Siglo XXI
2024
Mexican Social Security Institute
2024
Hospital de Especialidades
2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2017-2023
National Institutes of Health
2017-2023
Pediatrics and Genetics
2018-2022
Eunice Kennedy Shriver Center
2022
Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease. To determine the mutational status FIPA and young patients, analyzing their clinical characteristics, perform AIPmut carrier family members. This was observational, longitudinal study conducted...
Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be causative gene, and c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested play a role pathogenesis of acromegaly. We studied 153 patients (58 females 95 males) with gigantism. mutation-negative cases were screened for duplication through copy number variation...
Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as most common genetic alteration patients with Cushing disease (CD). However, frequency of these pediatric population has not extensively assessed. We investigated status USP8 at somatic level a cohort corticotroph adenomas. The was fully sequenced both germline and tumor DNA samples from 42 CD. Clinical, biochemical, imaging data were compared between without mutations. Five different (three...
The CABLES1 cell cycle regulator participates in the adrenal–pituitary negative feedback, and its expression is reduced corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated presence of mutations/copy number variations (CNVs) their associated clinical, histopathological molecular features patients Cushing’s disease (CD). Samples from 146 pediatric (118 germline DNA only/28 tumor DNA) 35 adult (tumor CD were screened for mutations. CNVs assessed 116 (87...
Abstract Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting to clinical characteristics AIPmut AIPneg patients. Design 12-year prospective, observational study. Participants & Setting We studied probands...
Abstract Background Somatic mutations in the ubiquitin-specific peptidase 8 (USP8) gene are common corticotropinomas of children with Cushing disease (CD). We report a unique patient germline USP8 mutation who presented CD and constellation other findings that constitute an intriguing genetic syndrome. Case Description describe 16-year-old female CD, developmental delay, dysmorphic features, ichthyosiform hyperkeratosis, chronic lung disease, kidney hyperglycemia, dilated cardiomyopathy...
Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts a large number independent proteins three chaperone systems, HSP90, HSP70 TOMM20. We determined structure TPR domain at high resolution, which has allowed detailed analysis how disease-associated mutations impact on structural integrity...
Known germline gene abnormalities cause one-fifth of the pituitary adenomas in children and adolescents, but, contrast with other tumor types, genetic causes corticotropinomas are largely unknown. In this study, we report a case Cushing disease (CD) due to loss-of-function mutation PRKAR1A, providing evidence for association corticotropinoma. A 15-year-old male presenting hypercortisolemia was diagnosed CD. Remission achieved after surgical resection corticotropin (ACTH)-producing...
The pathogenic effect of mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene (AIPmuts) pituitary adenomas is incompletely understood. We have identified primary mechanism loss function for missense AIPmuts. This study sought to analyze mechanism/speed turnover wild-type and AIP variants, correlating half-life with clinical parameters. Half-life protein–protein interaction experiments cross-sectional analysis AIPmut positive patients' data were performed a academic...
Abstract Context Germline loss-of-function CDKN1B gene variants cause the autosomal dominant syndrome of multiple endocrine neoplasia type 4 (MEN4). Even though pituitary neuroendocrine tumors are a well-known component syndrome, only 2 cases Cushing’s disease (CD) have so far been described in this setting. Aim To screen large cohort CD patients for defects and to determine their functional effects. Patients We screened 211 (94.3% pediatric) by germline whole-exome sequencing (WES) (n =...
Introduction Patients with neurofibromatosis type 1 (NF1) are at risk for developing various neoplasms. Since the early twentieth century, multiple cases of pituitary neuroendocrine tumors (PitNETs) occurring in this context have been published. Yet, role NF1 (17q11.2) loss-of-function (LOF) variants tumorigenesis remains unclear. Aim We report clinical and molecular characterization a case PitNET diagnosed patient NF1. also review available data against causal association between defects...
Genetic tests are part of the routine clinical approach to syndromic and nonsyndromic phenotypes neuroendocrine neoplasms (NENs). Current data on phenotype-genotype associations in NENs, however, do not accurately represent all populations. To describe frequency, inventory, germline defects associated with multiple types NENs a Mexican cohort. Blood DNA from adults was analyzed 53-gene NGS panel developed ad hoc (n=90) or Sanger sequencing (n=2). Single nucleotide variants, indels structural...
Abstract Objective Heterozygous germline loss-of-function variants in AIP are associated with young-onset growth hormone and/or prolactin-secreting pituitary tumours. However, the pathogenic role of c.911G>A; p.(Arg304Gln) (R304Q) variant has been controversial. Recent data from public exome/genome databases show this is not infrequent. The objective work was to reassess pathogenicity R304Q based on clinical, genomic and functional assay data. Design, materials methods Data were...
Introduction Pituitary adenomas (PAs) are common, usually benign tumors of the anterior pituitary gland which, for most part, have no known genetic cause. PAs associated with major clinical effects due to hormonal dysregulation and tumoral impingement on vital brain structures. PAM encodes a multifunctional protein responsible essential C-terminal amidation secreted peptides. Methods Following identification loss-of-function variant (p.Arg703Gln) in peptidylglycine a-amidating monooxygenase...
Background Predictive tools to identify patients at risk for gene mutations related pituitary adenomas are very helpful in clinical practice. We therefore aimed develop and validate a reliable category system aryl hydrocarbon receptor-interacting protein ( AIP ) with adenomas. Methods An international cohort of 2227 subjects were consecutively recruited between 2007 2016, including (familial sporadic) their relatives. All probands (n=1429) screened mutations, those diagnosed adenoma...
// Laura C. Hernández-Ramírez 1, 4 , Rhodri M.L. Morgan 2, 5 Sayka Barry 1 Fulvio D’Acquisto 3 Chrisostomos Prodromou 2 and Márta Korbonits Centre for Endocrinology, Barts The London School of Medicine, Queen Mary University London, EC1M 6BQ, UK Genome Damage Stability Centre, Sussex, Brighton, Falmer, BN1 9RQ, Microvascular Research, Present address: Section on Endocrinology Genetics, Eunice Kennedy Shriver National Institute Child Health Human Development...
Genomic losses/gains are associated with cancer progression and prognosis. In pituitary adenomas, analyses of copy number variations (CNVs) have shown that a subset adenomas higher genomic variability. However, whether CNVs tumor aggressiveness prognosis has not been determined. We hypothesized somatic tumors may play role in the corticotropinomas children adolescents. Paired germline DNA samples from 27 pediatric patients Cushing disease (CD), were subjected to whole exome sequencing....