title: Failure of tooth eruption and brachydactyly in pseudohypoparathyroidism are not related to plasma parathyroid hormone-related protein levels.
abstract: BACKGROUND
  Pseudohypoparathyroidism (PHP) is a genetic disorder characterized by resistance to the peripheral action of PTH due to maternally inherited heterozygous inactivating mutations in the coding sequence of Gsα or intronic regions of GNAS leading to aberrant splice variants (PHP1A), or methylation defects at GNAS (PHP1B). Brachydactyly is a clinical feature associated with both PHP1A and PHP1B, although it is more frequent in PHP1A patients. Loss-of-function mutations in PTHLH, the gene coding for parathyroid hormone related protein (PTHrP) were previously described in some patients with brachydactyly. Primary failure of tooth eruption (PFE) is related to some syndromes involving skeletal development, but it is also known as a nonsyndromic autosomal dominant condition. Previous studies showed that familial nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor (PTH1R) for PTH and PTHrP. Thus, we hypothesized that PTHrP resistance could result in failure of tooth eruption (FTE) and/or brachydactyly in PHP.
  
  
  METHODS
  Nineteen patients with a molecular diagnosis of PHP underwent dental panoramic radiography (DPR), hand radiography and had their PTHrP levels measured. Patients with alterations at DPR were submitted to clinical dental evaluation.
  
  
  RESULTS
  Nine patients had FTE and 7 patients had brachydactyly; 4 patients presented both features and none of them presented high PTHrP levels. Fourteen patients had PTHrP levels within the normal range and only one patient had slightly elevated PTHrP levels. Additionally, three novel GNAS mutations were described.
  
  
  CONCLUSIONS
  We described the dental abnormalities in a large series of PHP patients that were followed in a single tertiary center. No relationship between plasma PTHrP levels and failure of tooth eruption, dental manifestations of PHP or brachydactyly was found. It is important that doctors pay attention to dental manifestations of the disease in order to refer patients to a proper care with dentists.
authors: Osteometabolic Disorders Unit, Hormone and Molecular Genetics Laboratory (LIM-42), Endocrinology Department, Hospital das Clínicas, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, Prédio dos ambulatórios (PAMB), 8° andar, Bloco 3, CEP: 05403-900, São Paulo, SP, Brazil. Electronic address: marianareis@gmail.com.
authors: Mariana Tenorio Antunes
authors: MT
authors: Reis
authors: Dentistry Division, Hospital das Clínicas, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, PAMB, 6° andar, Bloco 2, CEP: 05403-900, São Paulo, SP, Brazil. Electronic address: diogo.matias@hc.fm.usp.br.
authors: Diogo Toledo
authors: DT
authors: Matias
authors: Dentistry Division, Hospital das Clínicas, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, PAMB, 6° andar, Bloco 2, CEP: 05403-900, São Paulo, SP, Brazil. Electronic address: mejfaria@uol.com.br.
authors: Maria Estela Justamante de
authors: ME
authors: Faria
authors: Osteometabolic Disorders Unit, Hormone and Molecular Genetics Laboratory (LIM-42), Endocrinology Department, Hospital das Clínicas, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, Prédio dos ambulatórios (PAMB), 8° andar, Bloco 3, CEP: 05403-900, São Paulo, SP, Brazil. Electronic address: reginamm@usp.br.
authors: Regina Matsunaga
authors: RM
authors: Martin
mesh_terms: D000328:Adult; D059327:Brachydactyly / Q000097:blood* / Q000150:complications*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D011547:Pseudohypoparathyroidism / Q000097:blood* / Q000150:complications*; D014078:Tooth Eruption; D055815:Young Adult
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein
keywords: Brachydactyly; Failure of tooth eruption; Parathyroid hormone related protein (PTHrP); Pseudohypoparathyroidism