{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:17:49Z","timestamp":1791011869777,"version":"4.1.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The predominant feature of pseudohypoparathyroidism (PHP) is renal resistance to PTH. Pseudohypoparathyroidism type Ia (PHP-Ia) is caused by maternally inherited heterozygous mutations in the GNAS exons encoding the \u03b1-subunit of the stimulatory G protein (Gs\u03b1). Besides PTH resistance, PHP-Ia patients have Albright\u2019s hereditary osteodystrophy and often display resistance to additional hormones. Patients with PHP-Ib lack features of Albright\u2019s hereditary osteodystrophy, and PTH resistance is associated with loss of methylation at the maternal GNAS exon A\/B. Most individuals with the autosomal dominant form of PHP-Ib have a 3-kb microdeletion within STX16 approximately 220 kb upstream of exon A\/B. Here we report on the clinical and genetic aspects of a Greek PHP-Ib kindred with four affected members and three obligate carriers, who had the 3-kb deletion within STX16. Symptomatic hypocalcemia was present only in the proband, but PTH was elevated in all members who had inherited the 3-kb deletion maternally. In all affected family members, urinary phosphate excretion was normal, but 1,25-dihydroxyvitamin D levels were diminished. These findings confirm previous data regarding patient to patient variation in disease severity for autosomal dominant PHP-Ib. Furthermore, affected individuals displayed hypouricemia with increased fractional excretion of uric acid, suggesting possible involvement of PTH in the renal handling of this metabolite.<\/jats:p>","DOI":"10.1210\/jc.2004-0249","type":"journal-article","created":{"date-parts":[[2004,12,3]],"date-time":"2004-12-03T18:47:38Z","timestamp":1102099658000},"page":"5942-5947","source":"Crossref","is-referenced-by-count":47,"title":["Phenotypic and Molecular Genetic Aspects of Pseudohypoparathyroidism Type Ib in a Greek Kindred: Evidence for Enhanced Uric Acid Excretion Due to Parathyroid Hormone Resistance"],"prefix":"10.1210","volume":"89","author":[{"given":"Elena","family":"Laspa","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, University of Ioannina (E.L., A.T.), 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Bastepe","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital (M.B., H.J.), Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Ju\u0308ppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, Massachusetts General Hospital (M.B., H.J.), Massachusetts 02114"},{"name":"Pediatric Nephrology (H.J.), MassGeneral Hospital for Children, and Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathocles","family":"Tsatsoulis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, University of Ioannina (E.L., A.T.), 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616260826800_R1","first-page":"1137","article-title":"Pseudohypoparathyroidism","author":"Levine","year":"2002","journal-title":"In: Bilezikian JP, Raisz, LG, Rodan GA, eds. Principles of bone biology. New York: Academic Press;"},{"key":"2020071616260826800_R2","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1210\/jc.2003-031271","article-title":"Pseudohypoparathyroidism and mechanisms of resistance toward multiple hormones: molecular evidence to clinical presentation.","volume":"88","author":"Bastepe","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616260826800_R3","first-page":"675","article-title":"Endocrine manifestations of stimulatory G protein \u03b1-subunit mutations and the role of genomic imprinting.","volume":"22","author":"Weinstein","year":"2001","journal-title":"Endocr Rev"},{"key":"2020071616260826800_R4","first-page":"1560","article-title":"Heterogeneous mutations in the gene encoding the \u03b1-subunit of the stimulatory G protein of adenyl cyclase in Albright\u2019s hereditary osteodystrophy.","volume":"76","author":"Miric","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616260826800_R5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/jmg.30.2.101","article-title":"Imprinting in Albright\u2019s hereditary osteodystrophy.","volume":"30","author":"Davies","year":"1993","journal-title":"J Med Genet"},{"key":"2020071616260826800_R6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0889-8529(05)70151-1","article-title":"Pseudohypoparathyroidism: new insights into an old disease.","volume":"29","author":"Bastepe","year":"2000","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071616260826800_R7","doi-asserted-by":"crossref","first-page":"11798","DOI":"10.1073\/pnas.95.20.11798","article-title":"The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3.","volume":"95","author":"Ju\u0308ppner","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071616260826800_R8","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1359\/jbmr.2003.18.3.424","article-title":"The pseudohypoparathyroidism type Ib locus is linked to a region including GNAS1 at 20q13.3.","volume":"18","author":"Jan de Beur","year":"2003","journal-title":"J Bone Miner Res"},{"key":"2020071616260826800_R9","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI10431","article-title":"A GNAS1 imprinting defect in pseudohypoparathyroidism type Ib.","volume":"106","author":"Liu","year":"2000","journal-title":"J Clin Invest"},{"key":"2020071616260826800_R10","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/hmg\/10.12.1231","article-title":"Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A\/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus.","volume":"10","author":"Bastepe","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2020071616260826800_R11","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1172\/JCI19159","article-title":"Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS.","volume":"112","author":"Bastepe","year":"2003","journal-title":"J Clin Invest"},{"key":"2020071616260826800_R12","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1073\/pnas.95.15.8715","article-title":"Variable and tissue-specific hormone resistance in heterotrimeric Gs protein \u03b1-subunit (Gs\u03b1) knockout mice is due to tissue-specific imprinting of the Gs\u03b1 gene.","volume":"95","author":"Yu","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071616260826800_R13","first-page":"F507","article-title":"Variable imprinting of the heterotrimeric G protein Gs\u03b1-subunit 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