Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.23 (
beta-galactosidase
)
14,648
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the
aryl hydrocarbon receptor interacting protein
(
AIP
) gene have been reported in 15-40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the
AIP
gene. We describe a large cohort of FIPA families and characterize missense and silent mutations using minigene constructs, luciferase and
beta-galactosidase
assays, as well as in silico predictions. Patients with
AIP
mutations had a lower mean age at diagnosis (23.6+/-11.2 years) than
AIP
mutation-negative patients (40.4+/-14.5 years). A promoter mutation showed reduced in vitro activity corresponding to lower mRNA expression in patient samples. Stimulation of the protein kinase A-pathway positively regulates the
AIP
promoter. Silent mutations led to abnormal splicing resulting in truncated protein or reduced
AIP
expression. A two-hybrid assay of protein-protein interaction of all missense variants showed variable disruption of
AIP
-phosphodiesterase-4A5 binding. In summary, exonic, promoter, splice-site, and large deletion mutations in
AIP
are implicated in 31% of families in our FIPA cohort. Functional characterization of
AIP
changes is important to identify the functional impact of gene sequence variants.
...
PMID:Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. 2050 37
