Clinical, biochemical, and genetic analysis of Korean patients with pseudohypoparathyroidism type Ia

Pseudohypoparathyroidism (PHP) comprises a heterogeneous group of endocrine disorders with the common feature of resistance to parathormone (PTH), manifested by hypocalcemia, hyperphosphatemia, and elevation o-f serum PTH despite normal renal function. Herein, the first Korean cases of PHP type Ia are reported. The two patients (6-yr-old female, 7-yr-old male) had typical signs of Albright hereditary osteodystrophy. Genomic DNA was isolated from their peripheral blood leukocytes and the GNAS gene was amplified by PCR and analysed by bidirectional sequencing including all coding exons. Two GNAS mutations were found: c.94A>T and c.344-345insT. Patient 1 had a nonsense mutation of c.94A>T (p. K32X), which has not been previously described; the mother also had c.94A>T, and it therefore was a familial mutation. Patient 2 had a known frame shift mutation for c.344-345insT (p.V117RfsX23). The family members of patient 2 had wild-type sequences. In summary, two Korean patients with PHP-Ia were confirmed by genetic analysis and a novel p.K32X product of the GNAS mutation was identified.