Pseudohypoparathyroidism Ib (PHP-Ib) is associated with methylation changes at differentially methylated regions (DMRs) within the complex GNAS locus, located at 20q13.2-13.3, gives rise different transcripts according to parental origin of the allele. PHP-Ib familial form is defined by an isolated loss of methylation at the A/B DMR, secondary to deletion in the STX16 gene. However the cause of the GNAS diffuse imprinting defects in sporadic PHP-Ib remains understood. Epigenetic changes mimic the paternal-specific methylation pattern. Uniparental disomy (UPD) is when both copies of a chromosome are from one parent only. Thus, paternal UPD of chromosome 20 (patUPD20) is a plausible cause of PHP-Ib. We screened a cohort of 53 patients presenting sporadic PHP-Ib to evaluate the frequency of patUPD20. CGH+SNP-array was used to identify copy neutral (absence of copy number variant) with loss of heterozygosity (cnLOH). Comparison of STR along chromosome 20 between the proband and his parents were used to confirm cnLOH and patUPD20. We also detailed phenotype of patients. Because CGH+SNP-array required high quality DNA, only 20 samples were tested. We found 5 patients (25%) with patUPD20: 3 complete patUPD20, 1 patUPD of the long arm of chromosome 20 and 1 with an interstitial UPD including GNAS locus. Patients with patUPD20 are not different of patients without patUPD20. Up to day, few isolated cases of patUPD20 have been published and our study suggests that patUPD20 is a frequent cause of PHP-Ib that is important for genetic counseling and should be tested in evaluation of patients with sporadic PHP-Ib.Le texte complet de cet article est disponible en PDF.