An intronic mutation is associated with prolactinoma in a young boy, decreased penetrance in his large family, and variable effects on MEN1 mRNA and protein

Abstract

Prolactinomas are rare tumors in prepubertal children. A prolactinoma in a young child may be due to sequence variants in genes that are known to cause these tumors (MEN1, PRKAR1A, AIP). An 11-year-old boy with a macroprolactinoma was treated with cabergoline and the tumor receded. We studied the patient and his family for genetic causes of this tumor. No mutations were present in the coding sequence of PRKAR1A and AIP. A novel heterozygous substitution (IVS3-7 c>a) was identified in intron 3 of MEN1. We also found an additional PCR amplicon that incorporated the entire intron 3 of the gene (210bp) in the patient's cDNA. The same amplicon was present with lower intensity in some of the control individuals who were not mutation carriers. Intron 3 harbors an in-frame stop codon and its incorporation is predicted to result in a prematurely terminated protein. We conclude that a novel MEN1 variation was identified in a young boy with prolactinoma and six of his relatives who did not presen