Pseudohypoparathyroïdies : hétérogénéité clinique et moléculaire.

Abstract

Les pseudohypoparathyroidies (PHP) correspondent a diverses situations clinico-biologiques caracterisees par la resistance des tissus cibles a la parathormone (PTH). On en distingue plusieurs varietes selon l' existence ou non d' un phenotype dysmorphique et de resistances a d' autres hormones, et selon les reponses des voies de signalisation hormonale a l' apport exogene de PTH. La PHP Ia, qui associe osteodystrophie d' Albright et resistances hormonales multiples, resulte d' une anomalie du gene GNAS1 qui code pour la sous-unite a de la proteine G stimulatrice. L' osteodystrophie d' Albright isolee est appelee pseudopseudohypoparathyroidie et s' explique aussi par un defaut du gene GNAS1. Cette variabilite phenotypique semble liee a une empreinte genomique paternelle. Dans la PHP Ib, caracterisee par la seule resistance a la PTH (sans dysmorphie ni resistance multiple), une anomalie d' un promoteur du gene du recepteur de la PTH est le plus souvent evoquee. Plus rares, les PHP Ic et II seraient liees a un defaut de la transmission du signal en aval de la proteine G.

Syndromes of pseudohypoparathyroidism (PHP) include several pathological conditions mostly characterized by target tissues resistance to parathormone (PTH). They are classified according to the occurrence of a particular phenotype (Albright's osteodystrophy) and multiple hormone resistance, and effector response to exogenic PTH administration. PHP type Ia associates Albright's osteodystrophy and multiple hormone resistance. It results from abnormal GNAS1 gene, which encodes the alpha sub-unit of the stimulatory G protein. Isolated Albright osteodystrophy, without biological abnormalities of resistance to PTH, is called pseudopseudohypoparathyroidism and is also linked to a defect of the GNAS1 gene. This phenotypic variability seems to be related to paternal genomic imprinting of the gene. PHP type Ib is characterized by isolated resistance to PTH (without dysmorphy and multiple hormone resistance). Its genetic defect is not precisely determined but an anomaly of a promoter regulating PTH receptor gene is frequently suggested. Infrequent, PHP type Ic and II could be related to a defect of signal transduction, downstream of G protein.