Pseudohypoparathyroidism (PHP) type 1 is an autosomal dominant disorder characterized by biochemical hypoparathyroidism due to resistance of target tissues to parathyroid hormone (PTH). Two fundamentally different forms of PHP type 1 have been described. In PHP type 1a, mutations in the GNAS1 gene lead to reduced expression or activity of the (alpha subunit of the G protein (Gs-alpha) that couples heptahelical receptors for PTH and many other hormones to activation of adenylyl cyclase. Accordingly, widespread deficiency of Gs-alpha is associated with resistance not only to PTH but also to other hormones that act by stimulating adenylyl cyclase. By contrast, Gs-alpha is normal in PHP type 1b, and hormone resistance is limited to PTH target tissues. These observations had suggested that the defect in PHP type 1b was the type 1 PTH receptor, but molecular analysis of this gene has not revealed mutations. The goal of this project is to identify and characterize the gene for PHP type 1b using linkage analysis and a candidate gene approach. The GCRC is used to evaluate the endocrine and metabolic characteristics of patients with PHP type 1 in order to determine whether they have the type 1a or type 1b variant. Subjects who meet the criterion for PHP type 1b will undergo a comprehensive analysis of their family in order to recruit all affected and unaffected relatives. Genomic DNA samples will be obtained from all familial and sporadic cases in order to perform the genetic linkage analyses and to test candidate genes. Once the PHP1b gene is identified, the long-range goal will be to characterize the function of the gene product, to examine genotype-phenotype correlations, and to understand its role in regulating expression or action of the PTH receptor in health and disease.
| Altekruse, Sean F; Shiels, Meredith S; Modur, Sharada P et al. (2018) Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS 32:513-521 |
| Salemi, Parissa; Skalamera Olson, Julie M; Dickson, Lauren E et al. (2018) Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype, Inheritance, Sex, Age, Hormonal Status, and BMI. J Clin Endocrinol Metab 103:158-168 |
| Robert Braši?, James; Mari, Zoltan; Lerner, Alicja et al. (2018) Remission of Gilles de la Tourette Syndrome after Heat-Induced Dehydration. Int J Phys Med Rehabil 6: |
| Altman, Matthew C; Whalen, Elizabeth; Togias, Alkis et al. (2018) Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma. J Allergy Clin Immunol 142:1856-1866 |
| AIDS-defining Cancer Project Working Group of IeDEA, COHERE in EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. AIDS 32:2777-2786 |
| Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671 |
| Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72 |
| Al-Sofiani, Mohammed E; Yanek, Lisa R; Faraday, Nauder et al. (2018) Diabetes and Platelet Response to Low-Dose Aspirin. J Clin Endocrinol Metab 103:4599-4608 |
| Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429 |
| Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451 |
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