Searching for Arg201 mutations in the GNAS1 gene in Italian patients with McCune-Albright syndrome.
McCune-Albright syndrome (MAS) is a rare disease caused by somatic postzygotic mutations at Arg201 in the GNAS1 gene that encodes for the Gsalpha protein. Arg201 mutations are gain-of-function mutations in affected tissues (including bone, skin, endocrine glands and other tissues) that result in the activation of cAMP. We used a polymerase chain reaction(PCR)-based technique for the selective enrichment and analysis of the Arg201 mutant allele in 27 different tissues from 24 Italian patients with one or more signs of MAS. Arg201 mutations were identified in 13 different tissues (48.1%) from 11 patients (45.8%). Mutation detection rates differed across the various types of tissue samples, and the mutation was not always found in every tissue sample from the same patient. To overcome problems in the analysis of mutations in somatic mosaicism, as occurs in MAS, a highly sensitive molecular technique should be applied, the most appropriate tissue source selected, and various affected tissues from the same patient analyzed.
Department of Pediatrics, University of Torino, Regina Margherita Children's Hospital, Italy. ldesanct@pediatria.unito.it
Luisa
L
de Sanctis
Damiano
D
Romagnolo
Nella
N
Greggio
Lorenzo
L
Genitori
Roberto
R
Lala
Carlo
C
de Sanctis
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001120:Arginine; D019205:GTP-Binding Protein alpha Subunits, Gs