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A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis
Various inactivating mutations in guanine nucleotide−binding protein, alpha−stimulating activity polypeptide1 (GNAS1) gene have been described with poor phenotype correlation. Pseudohypoparathyroidism type 1a (PHP1a) results from an inactivating mutation in the GNAS1 gene. Hormone resistance occurs...
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Formato: | Texto |
Lenguaje: | English |
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Galenos Publishing
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005748/ https://www.ncbi.nlm.nih.gov/pubmed/21274302 http://dx.doi.org/10.4274/jcrpe.v1i5.244 |
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author | Lubell, Tamar Garzon, Maria Anyane−Yeboa, Kwame Shah, Bina |
author_facet | Lubell, Tamar Garzon, Maria Anyane−Yeboa, Kwame Shah, Bina |
author_sort | Lubell, Tamar |
collection | PubMed |
description | Various inactivating mutations in guanine nucleotide−binding protein, alpha−stimulating activity polypeptide1 (GNAS1) gene have been described with poor phenotype correlation. Pseudohypoparathyroidism type 1a (PHP1a) results from an inactivating mutation in the GNAS1 gene. Hormone resistance occurs not only to parathyroid hormone (PTH), but typically also to other hormones which signal via G protein coupled receptors including thyroid stimulating hormone (TSH), gonadotropins, and growth hormone releasing hormone. In addition, the phenotype of Albright hereditary osteodystrophy (AHO) is observed, which may include short stature, round facies, brachydactyly, obesity, ectopic soft tissue or dermal ossification (osteoma cutis) and psychomotor retardation with variable expression. We present a 2−year−old boy with PHP 1A who initially presented at age 3 weeks with congenital hypothyroidism. By 17 months of age, he manifested osteoma cutis, psychomotor retardation, obesity, brachydactyly and resistance to PTH with normocalcemia and mild hyperphosphatemia. Genetic analysis revealed a novel mutation in exon 13 of GNAS1 in our patient. This mutation, c.1100_1101insA, resulted in a frameshift and premature truncation of bases downstream. This mutation was also found in the mother of this patient who was also noted to have short stature, obesity, brachydactyly and non progressive osteoma cutis, but no hormone resistance. We report a novel heterozygous mutation causing PHP1A with PTH and TSH resistance and AHO which has not been described previously. PHP1A is also a rare presentation of congenital hypothyroidism. Conflict of interest:None declared. |
format | Text |
id | pubmed-3005748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Galenos Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-30057482011-01-27 A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis Lubell, Tamar Garzon, Maria Anyane−Yeboa, Kwame Shah, Bina J Clin Res Pediatr Endocrinol Case Reports Various inactivating mutations in guanine nucleotide−binding protein, alpha−stimulating activity polypeptide1 (GNAS1) gene have been described with poor phenotype correlation. Pseudohypoparathyroidism type 1a (PHP1a) results from an inactivating mutation in the GNAS1 gene. Hormone resistance occurs not only to parathyroid hormone (PTH), but typically also to other hormones which signal via G protein coupled receptors including thyroid stimulating hormone (TSH), gonadotropins, and growth hormone releasing hormone. In addition, the phenotype of Albright hereditary osteodystrophy (AHO) is observed, which may include short stature, round facies, brachydactyly, obesity, ectopic soft tissue or dermal ossification (osteoma cutis) and psychomotor retardation with variable expression. We present a 2−year−old boy with PHP 1A who initially presented at age 3 weeks with congenital hypothyroidism. By 17 months of age, he manifested osteoma cutis, psychomotor retardation, obesity, brachydactyly and resistance to PTH with normocalcemia and mild hyperphosphatemia. Genetic analysis revealed a novel mutation in exon 13 of GNAS1 in our patient. This mutation, c.1100_1101insA, resulted in a frameshift and premature truncation of bases downstream. This mutation was also found in the mother of this patient who was also noted to have short stature, obesity, brachydactyly and non progressive osteoma cutis, but no hormone resistance. We report a novel heterozygous mutation causing PHP1A with PTH and TSH resistance and AHO which has not been described previously. PHP1A is also a rare presentation of congenital hypothyroidism. Conflict of interest:None declared. Galenos Publishing 2009-09 2009-08-06 /pmc/articles/PMC3005748/ /pubmed/21274302 http://dx.doi.org/10.4274/jcrpe.v1i5.244 Text en © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Case Reports Lubell, Tamar Garzon, Maria Anyane−Yeboa, Kwame Shah, Bina A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis |
title | A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis |
title_full | A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis |
title_fullStr | A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis |
title_full_unstemmed | A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis |
title_short | A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis |
title_sort | novel mutation causing pseudohypoparathyroidism 1a with congenital hypothyroidism and osteoma cutis |
topic | Case Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005748/ https://www.ncbi.nlm.nih.gov/pubmed/21274302 http://dx.doi.org/10.4274/jcrpe.v1i5.244 |
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