Bone Abstracts

Objects: Seventy seven clinically diagnosed pseudohypoparathyroidism (PHP) patients from our hospital during 2000–2010 were recruited to analyze the clinical features and molecular genetics of Chinese PHP patients.

Methods: The clinical data of the 77 PHP patients were retrospectively analyzed. Methylation status of GNAS was detected by combined bisulfiterestriction analysis. Genome DNA was extracted from peripheral blood lymphocytes. GNAS gene mutation was screened by PCR and Sanger sequencing. The study was approved by the local Ethics Committee of our center.

Results: There were 17 PHP-Ia patients with normal methylation in all four Differentially Methylated Region (DMRs), 13 familial PHP-Ib patients with loss of methylation in A/B, and 47 sporadic PHP-Ib patients with broad GNAS methylation changes according to combined bisulfiterestriction analysis. Furthermore, 3.0 kb deletion in STX16 were identified in nine familial PHP-1b patients with no 4.4 kb deletion in the same locus found. There were three new GNAS mutations (c. 314-316 del AAG, ins T c.352 insC, VS12+1G>T) identified in PHP-1a individuals. Among all the subjects, the average serum calcium was 1.74±0.29 mM and the mean PTH level was 371.8±223.8 pg/ml at the first visit to our center. AHO phenotype existed in all PHP-1a patients but only 57.4% of sporadic PHP-1b and 44.4% of familial PHP-1b patients respectively. Among the 41 subjects with results of thyroid function, TSH resistance was detected in 6/6 (100%) of PHP-1a, 10/27 (37.0%) of sporadic PHP1b, and 1/6 (16.7%) of familial PHP1b patients.

Conclusion: Clinical presentation may overlap among the three kinds of PHP individuals despite earlier onset and higher incidence of AHO and TSH resistance in PHP 1a, while the underlying molecular genetics are totally different. Thus careful molecular and epigenetic analysis are necessary to make the right diagnosis.