Abstract | OBJECTIVE: METHODS: Thirteen unrelated families (8 with PHPIa and PPHP patients, and 5 with PPHP patients only) were investigated for GNAS1 mutations in the 1050 base-pair (bp) region spanning exons 2-13 by single-stranded conformational polymorphism (SSCP) and DNA sequence analysis. RESULTS: GNAS1 mutations were detected in 4 of the 8 families with PHPIa patients. These consisted of: two novel de novo missense mutations (Pro115Ser and Glu259Val) in two families and an identical 4 bp deletion of codons 189 and 190 resulting in a frame-shift in two unrelated families. These results expand the spectrum of GNAS1 mutations associated with this disorder and confirm the presence of a mutational hot-spot involving codons 189 and 190. SSCP analysis was found to be a specific and sensitive method that detected all 4 mutations. GNAS1 mutations were not detected in any of the PPHP only families. CONCLUSIONS: The pseudohypoparathyroid disorders appear to represent a heterogeneous group with GNAS1 mutations forming the molecular aetiology in approximately 50% of pseudohypoparathyroidism type Ia families. Such mutations can be reliably identified by single-stranded conformational polymorphism and this will help to supplement the clinical evaluation of some patients and their families, particularly as the disease may not be fully penetrant.
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Authors | S F Ahmed, P H Dixon, D T Bonthron, H F Stirling, D G Barr, C J Kelnar, R V Thakker |
Journal | Clinical endocrinology
(Clin Endocrinol (Oxf))
Vol. 49
Issue 4
Pg. 525-31
(Oct 1998)
ISSN: 0300-0664 [Print] England |
PMID | 9876352
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protein Isoforms
- DNA
- GTP-Binding Protein alpha Subunits, Gs
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Topics |
- Adolescent
- Adult
- Child
- Child, Preschool
- DNA
(genetics)
- DNA Mutational Analysis
- Female
- Frameshift Mutation
- GTP-Binding Protein alpha Subunits, Gs
(genetics)
- Humans
- Male
- Mutation, Missense
- Pedigree
- Polymorphism, Single-Stranded Conformational
- Protein Isoforms
- Pseudohypoparathyroidism
(genetics)
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