5573

PRKAR1A

ADOHR|CAR|CNC|CNC1|PKR1|PPNAD1|PRKAR1|TSE1;protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1);PRKAR1A;protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)

cAMP-dependent protein kinase regulatory subunit RIalpha|cAMP-dependent protein kinase type I-alpha regulatory chain|cAMP-dependent protein kinase type I-alpha regulatory subunit|protein kinase A type 1a regulatory subunit|tissue-specific extinguisher 1

17q23-q24

protein-coding

Recent molecular genetic investigations of primary cardiac tumors (myxomas, lipomas, rhabdomyomas, and fibromas) have provided insight into fundamental mechanisms of cardiac cell growth. Myxomas are the most common adult cardiac tumor, and familial cardiac myxomas are now appreciated to be caused by mutations in the PRKAR1alpha gene that encodes a regulatory subunit of protein kinase A. Cytogenetic studies have targeted candidate chromosomal loci that may be perturbed during cardiac lipoma pathogenesis. Rhabdomyomas, the most common pediatric cardiac neoplasm, are frequently associated with tuberous sclerosis, caused by mutations in the TSC-1 and TSC-2 genes. The study of Gorlin syndrome has shed light on the etiology of cardiac fibromas. This disorder is caused by mutation of the PTC gene, which regulates cell growth, commitment and differentiation. In the future, manipulation of PRKAR1alpha-, TSC-, and PTC-dependent pathways may foster new strategies to regenerate myocardium in theischemic or myopathic heart.

Prolactinomas are rare tumors in prepubertal children. A prolactinoma in a youngchild 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 codingsequence 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 (210 bp) in the patient's cDNA. Thesame 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 present with prolactinoma or other MEN1 related symptoms. This novel MEN1 variation may be associated with low penetrance of the disease. The IVS3-7 c>a defect is suggested to be pathogenic because it is associated with lower menin levels in the cells of these patients,but its consequences may be mitigated by a variety of factors including changes in transcription and translation of the MEN1 gene.#CI- Copyright Georg Thieme Verlag KG Stuttgart. New York.