Mutational analysis of the GNAS1 exons encoding the stimulatory G protein in five patients with pseudohypoparathyroidism type 1a.
We analyzed the GNAS1 gene in five patients with pseudohypoparathyroidism type 1a (PHP1a) by performing polymerase chain reaction, followed by sequencing all 13 exons of the gene, single-stranded conformational polymorphism (SSCP) or heteroduplex analysis (HD). Three novel mutations were discovered: (1) a de novo 3 bp insertion of CTG in codon 47 of exon 1; (2) a missense mutation 1103T in exon 4; and (3) a de novo mutation of Arg280Gly in exon 10. Two other mutations, previously described in the literature, include: (1) a de novo 4 bp deletion (deltaGACT) involving codons 189 and 190 in exon 7, and (2) a deletion of a cytosine nucleotide at codon 115 in exon 5. We conclude that mutational analysis of the GNAS1 gene is a strong supportive tool for the diagnosis of PHP1a, and is a useful adjunct to the synthetic parathyroid hormone infusion test for PTH resistance.
Lim
Sharon H M
SH
Department of Paediatrics, National University of Singapore, Singapore.
Poh
Larry K S
LK
Cowell
Chris T
CT
Tey
Beng-Hea
BH
Loke
Kah-Yin
KY
D000293:Adolescent; D001210:Asia, Southeastern; D001315:Australia; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D011547:Pseudohypoparathyroidism / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019205:GTP-Binding Protein alpha Subunits, Gs