Purpose: Type I pseudohypoparathyroidism (PHP-I) can be subclassified into Ia and Ib, depending on the presence or absence of Albright's hereditary osteodystrophy's phenotype, diminished α-subunit of the stimulatory G protein (G(s)α) activity and multihormonal resistance. Whereas PHP-Ia is mainly associated with heterozygous inactivating mutations in G(s)α-coding exons of GNAS, PHP-Ib is caused by imprinting defects of GNAS. To date, just one patient with PHP and complete paternal uniparental disomy (UPD) has been described. We sought to identify the underlining molecular defect in twenty patients with parathyroid hormone resistance, hypocalcemia and hyperphosphatemia, and abnormal methylation pattern at GNAS locus.
Methods: Microsatellite typing and comparative genome hybridization were performed for proband and parents.
Results: We describe four patients with partial paternal UPD of chromosome 20 involving pat20qUPD in one case, from 20q13.13-qter in two cases, and pat20p heterodisomy plus interstitial 20q isodisomy in one patient.
Conclusions: These observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith-Wiedemann syndrome or neonatal diabetes.