A5047045725- Hypothalamic control of reproductive hormones
- Hormonal and reproductive studies
- Sexual Differentiation and Disorders
- Ovarian function and disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Growth Hormone and Insulin-like Growth Factors
- Pituitary Gland Disorders and Treatments
- Vitamin D Research Studies
- Pharmacology and Obesity Treatment
- Adrenal and Paraganglionic Tumors
- Adrenal Hormones and Disorders
- Muscle metabolism and nutrition
- Plant Reproductive Biology
- Hormonal Regulation and Hypertension
- Sperm and Testicular Function
- Sexual function and dysfunction studies
- Fibroblast Growth Factor Research
- Regulation of Appetite and Obesity
- Stress Responses and Cortisol
- Vitamin C and Antioxidants Research
- Parathyroid Disorders and Treatments
- Estrogen and related hormone effects
- Thyroid Disorders and Treatments
- Hemoglobinopathies and Related Disorders
- Neuroendocrine Tumor Research Advances
Imperial College London
2024-2025
Cumbria Northumberland Tyne and Wear NHS Foundation Trust
2024-2025
Newcastle upon Tyne Hospitals NHS Foundation Trust
2016-2025
Royal Victoria Infirmary
2016-2025
Mayo Clinic in Arizona
2025
Newcastle University
2015-2024
Hammersmith Hospital
2024
Newcastle upon Tyne Hospital
2013-2024
Walkergate Park Hospital
2024
University of Washington
2023
The lymphoid tyrosine phosphatase (LYP), encoded by the protein phosphatase-22 (PTPN22) gene, is a powerful inhibitor of T cell activation. Recently, single nucleotide polymorphism (SNP), encoding functional arginine to tryptophan residue change at LYP codon 620 has been shown be associated with type 1 diabetes and other autoimmune disorders. We have used PCR-restriction fragment (XcmI) assay examine genotypes in 549 unrelated probands Graves' disease, 104 subjects Addison's disease 429...
Idiopathic hypogonadotropic hypogonadism, which may be associated with anosmia (the Kallmann syndrome) or a normal sense of smell, is treatable form male infertility caused by congenital defect in the secretion action gonadotropin-releasing hormone (GnRH). Patients have absent incomplete sexual maturation age 18. hypogonadism was previously thought to require lifelong therapy. We describe 15 men whom reversal idiopathic sustained after discontinuation hormonal therapy.We defined as presence...
Idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome; KS) or a normal sense of smell (normosmic IHH; nIHH) are heterogeneous genetic disorders associated deficiency gonadotropin-releasing hormone (GnRH). While loss-of-function mutations in FGF receptor 1 (FGFR1) cause human GnRH deficiency, to date no specific ligand for FGFR1 has been identified neuron ontogeny. Using candidate gene approach, we 6 missense FGF8 IHH probands variable olfactory phenotypes. These...
Idiopathic hypogonadotropic hypogonadism (IHH) due to defects of gonadotropin-releasing hormone (GnRH) secretion and/or action is a developmental disorder sexual maturation. To date, several single-gene have been implicated in the pathogenesis IHH. However, significant inter- and intrafamilial variability apparent incomplete penetrance familial cases IHH are difficult reconcile with model defect. We therefore hypothesized that mutations at different loci interact some families modify their...
Between the genetic extremes of rare monogenic and common polygenic diseases lie diverse oligogenic disorders involving mutations in more than one locus each affected individual. Elucidating principles inheritance mechanisms interactions could help unravel newly appreciated role sequence variants disorders. With few exceptions, however, precise architecture remains unknown. Isolated gonadotropin-releasing hormone (GnRH) deficiency caused by defective secretion or action hypothalamic GnRH is...
Context: Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone involved tumorigenesis. Objective: AIP sequence changes and expression were studied FIPA sporadic adenomas. The function of normal mutated molecules was on cell proliferation protein-protein interaction. Cellular ultrastructural localization determined cells. Patients: Twenty-six kindreds 85...
Abstract Context: Mutations in TAC3 and TACR3 (encoding neurokinin B its receptor) have been identified Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations not yet tested genotype-phenotype correlations established. Objective: A broad cohort of normosmic IHH probands was screened for mutations TAC3/TACR3 to evaluate the prevalence such define genotype/phenotype relationships. Design Setting: The study consisted sequencing TAC3/TACR3, vitro functional...
Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition the reproductive axis stressors, but it unknown whether this variability reflects genetic predisposition amenorrhea. We hypothesized that mutations genes involved idiopathic hypogonadotropic hypogonadism, congenital GnRH...
OBJECTIVE The association of idiopathic hypogonadotrophic hypogonadism (IHH) with congenital olfactory deficit defines Kallmann's syndrome (KS). Although a small proportion IHH patients have been found to harbour defined genetic lesions, the basis most cases remains be elucidated. Genes currently recognized involved comprise KAL (associated X‐linked‐KS), GnRH receptor resistance therapy), DAX 1 adrenohypoplasia congenita) and three loci also associated obesity, leptin (OB), (DB) prohormone...
Mice deficient in prokineticin 2(PROK2) and receptor2 (PROKR2) exhibit variable olfactory bulb dysgenesis GnRH neuronal migration defects reminiscent of human deficiency.We aimed to screen a large cohort patients with Kallmann syndrome (KS) normosmic idiopathic hypogonadotropic hypogonadism (IHH) for mutations PROK2/PROKR2, evaluate their prevalence, define the genotype/phenotype relationship, assess functionality these mutant alleles vitro.Sequencing PROK2 PROKR2 genes was performed 170 KS...
The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it important to leverage the clinical evaluations KS patients prioritize screening.The objective study was determine which reproductive nonreproductive phenotypes subjects have implications for specific gene mutations.Two hundred nineteen were studied: 151 with identified rare sequence variants (RSVs) 8 genes known cause (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) 68 who remain RSV negative...
Neuronal development is the result of a multitude neural migrations, which require extensive cell-cell communication. These processes are modulated by extracellular matrix components, such as heparan sulfate (HS) polysaccharides. HS molecularly complex nonrandom modifications sugar moieties, including sulfations in specific positions. We report here mutations 6-O-sulfotransferase 1 ( HS6ST1 ) families with idiopathic hypogonadotropic hypogonadism (IHH). IHH manifests incomplete or absent...
A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation their hypothalamic-pituitary-gonadal axis normalization steroidogenesis and/or gametogenesis, a phenomenon termed reversal.The objective this study was to determine the natural history reversal and identify associated phenotypes genotypes.This retrospective review clinical, biochemical, genetic features IHH evaluated at an academic medical center.History spontaneous fertility, regular...
Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in human forebrain.The objective study was to investigate whether KS, CPHD, SOD have shared genetic origins.A total 103 patients with either CPHD (n = 35) or 68) were investigated for mutations genes implicated etiology KS (FGFR1, FGF8, PROKR2, PROK2, KAL1). Consequences identified FGFR1, PROKR2 vitro.Three had heterozygous FGFR1;...
Research Article13 April 2016Open Access Source DataTransparent process IGSF10 mutations dysregulate gonadotropin-releasing hormone neuronal migration resulting in delayed puberty Sasha R Howard Centre for Endocrinology, William Harvey Institute, Barts and the London School of Medicine Dentistry, Queen Mary University London, UK Search more papers by this author Leonardo Guasti Gerard Ruiz-Babot Alessandra Mancini Alessia David Integrative Systems Biology Bioinformatics, Department Life...
Objective Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth puberty (CDGP) represent rare common forms GnRH deficiency, respectively. Both CDGP CHH present with delayed puberty, the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while genetic basis poorly understood. Design We characterized compared architectures CDGP, to test hypothesis a shared disorders. Methods Exome...
Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with multidisciplinary approach treating patients MH. This has compiled using expertise from (medical nursing), primary care, clinical...