Home Page
References OMIM Gene GeneReviews HGMD HGNC
GENATLAS PHENOTYPE
last update : 30-11-2009
Symbol PHP1A
Location 20q13.32
Name pseudohypoparathyroism 1A
Corresponding gene GNAS
Main clinical features
  • hypocalcemia, hyperphosphatemia, and normal renal function, short stature, obesity, rounded face, short neck, and shortened metacarpals
  • clinical findings due to resistance to PTH rather than to PTH deficiency
  • either subclinical or clinical hypothyroidism due to resistance to TSH
  • multihormonal resistance and Albright’s hereditary osteodystrophy (AHO) characterized by round face, short neck, obesity, calcifications, brachydactyly, and/or mental retardation, defective erythrocyte Gs{alpha} activity (Fernandez-Rebollo 2010)
    • Genetic determination autosomal dominant
    Related entries Albright osteodystrophy (AHO)
    Function/system disorder osteo-articular
    Type malformation
    Gene product
    Name Gs alpha
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   under-expression maternally inherited inactivating mutation
    various types     mutation maternally and paternally transmitted
    Remark(s)
  • hot spot of mutation in exon 7
  • multiple endocrinopathies and low Gs alpha activities, parathyroid resistance is paternally imprinted, and any cases are inherited from a female affected by not any form, maybe also due to a potential isodisomy of chromosome 20q
  • same mutations inherited from the father lead to pseudo-PHP, in which AHO occurs in the absence of endocrine abnormalities ( Mantovani 2010)
    • Genotype/Phenotype correlations
  • mutation A366S leading to pseudohypoparathyroism 1A associated with testotoxicosis (activating mutation thermo-dependent, in scrotum, activating adenylyl cyclase, causing hormone-independent cAMP accumulation)
  • heterozygous 3 bp in frame deletion predicting a deletion of the asparagine residue at position 377 (deltaN377) associated to craniosynostosis (Graul-Neumann 2009)