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References OMIM Gene GeneReviews HGMD HGNC
last update : 26-05-2010
Symbol PHP1B
Location 20q13.32
Name pseudohypoparathyroidism, type 1B
Corresponding gene GNAS , STX16
Other symbol(s) PHPIB
Main clinical features
  • isolated renal resistance to PTH and sometimes mild TSH
  • resistance
  • parathyroid hormone-resistant hypocalcemia and hyperphosphatemia, increased serum PTH, without other endocrine anomalies or developmental defects
  • renal resistance to PTH and, in some cases, mild resistance to TSH in the absence of the AHO phenotype and resistance to other hormones
  • normal Gs{alpha} activity ( Fernandez-Rebollo 2010)
  • Genetic determination autosomal dominant
    Function/system disorder osteo-articular
    Type disease
    Gene mutationChromosome rearrangementEffectComments
    deletion   other deletion of a cis-acting imprinting control element that is necessary for establishing and/or maintaining methylation at GNAS exon A/B
    imprinting defect   unknown LOI at exon 1A
    deletion     microdeletions involving the STX16 gene appear to cause loss of methylation at exon A/B of the GNAS1 gene
  • also due to microdeletions involving the STX16 gene that cause loss of methylation at exon A/B of the GNAS1 gene
  • loss of exon A/B methylation combined with active A/B transcription from both parental alleles, leading to suppression of Gs alpha transcription in the proximal renal tubules and, therefore, PTH resistance
  • maternal loss of GNAS exon A/B methylation, leading to decreased Gs expression in specific tissues
  • most common defect is a loss of methylation in alternative exon A/B (also referred to as 1A) on the maternal allele, leading to biallelic expression of the A/B transcript (Fernandez-Rebollo 2010)