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 of 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.
Park
Chang-Hun
CH
Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, 135-710, Korea.
Park
Hyung-Doo
HD
Lee
Soo-Youn
SY
Kim
Jong-Won
JW
Sohn
Young Bae
YB
Park
Sung Won
SW
Jin
Dong-Kyu
DK
D019943:Amino Acid Substitution; D015992:Body Mass Index; D002648:Child; D002864:Chromogranins; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011547:Pseudohypoparathyroidism / Q000175:diagnosis / Q000235:genetics*
D002864:Chromogranins; D017931:DNA Primers; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs