title: Mutational analysis of the GNAS1 exons encoding the stimulatory G protein in five patients with pseudohypoparathyroidism type 1a.
abstract: 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.
authors.affiliation: Department of Paediatrics, National University of Singapore, Singapore.
authors.forename: Sharon H M
authors.initials: SH
authors.lastname: Lim
authors.forename: Larry K S
authors.initials: LK
authors.lastname: Poh
authors.forename: Chris T
authors.initials: CT
authors.lastname: Cowell
authors.forename: Beng-Hea
authors.initials: BH
authors.lastname: Tey
authors.forename: Kah-Yin
authors.initials: KY
authors.lastname: Loke
mesh_terms: 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
chemical_list: D019205:GTP-Binding Protein alpha Subunits, Gs