Disease relevance of Pseudopseudohypoparathyroidism

• Interestingly, paternal transmission of GNAS1 mutations leads to the AHO phenotype alone (pseudopseudohypoparathyroidism), while maternal transmission leads to AHO plus resistance to several hormones (e.g., PTH, TSH) that activate G(s) in their target tissues (pseudohypoparathyroidism type IA) [1].

High impact information on Pseudopseudohypoparathyroidism

• This is consistent with the presence of TSH resistance in patients with maternal G(s)alpha null mutations (PHP1A) and the absence of TSH resistance in patients with paternal G(s)alpha mutations (pseudopseudohypoparathyroidism) [2].
• An inherited mutation associated with functional deficiency of the alpha-subunit of the guanine nucleotide-binding protein Gs in pseudo- and pseudopseudohypoparathyroidism [3].
• STK25 is a candidate gene for pseudopseudohypoparathyroidism [4].
• The occurrence of pseudohypoparathyroidism/pseudopseudohypoparathyroidism (PH/PPH) and D brachydactyly (DB) in different persons in the same family is described for the first time [5].
• Maternal transmission of Gs(alpha) mutations leads to AHO plus resistance to several hormones (e.g., parathyroid hormone) that activate Gs in their target tissues (pseudohypoparathyroidism type IA), while paternal transmission leads only to the AHO phenotype (pseudopseudohypoparathyroidism) [6].

Chemical compound and disease context of Pseudopseudohypoparathyroidism

• The first case had all the metabolic abnormalities of pseudohypoparathyroidism; the second case had urinary cyclic adenosine-3',5'-monophosphate findings suggestive of pseudo-pseudohypoparathyroidism [7].

Gene context of Pseudopseudohypoparathyroidism

• AHO appears in patients with pseudohypoparathyroidism (PHP) who have resistance to PTH and in their eumetabolic family members who have pseudopseudohypoparathyroidism (PPHP) [8].
• Familial growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism [9].

References