This test analyzes the AIP gene, which is associated with familial isolated pituitary adenoma (FIPA). FIPA is a condition that causes an increased risk of developing noncancerous adenomas of the pituitary.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
AIP can also be ordered as part of a broader panel to test for different types of hereditary cancer. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered for no additional charge.
familial isolated pituitary adenoma (FIPA)
Pituitary adenoma (PA) is one of the most common types of intracranial tumors. PA is a type of noncancerous tumor that develops in the pituitary gland, a hormone-secreting gland in the brain. Familial isolated pituitary adenoma (FIPA) is characterized by the development of PA at a young age (primarily children, adolescents and young adults) and in the absence of any other abnormalities or health issues. The PA are often unusually large (macroadenoma) compared to sporadic cases.
Individuals with AIP-associated FIPA can develop any of several subtypes of pituitary adenomas, most of which secrete excessive amounts of certain hormones. Somatotropinomas are one of the most common types of PA seen in FIPA and cause overproduction of growth hormone. This can cause gigantism (consistent and excessive gain in height) and acromegaly (overgrowth of the face, hands and feet). Prolactinomas cause excessive prolactin that can result in abnormal menstruation, infertility and breast milk production in non-pregnant women; affected men may experience erectile dysfunction and in some cases, breast milk production. Some affected individuals may also develop nonfunctioning pituitary adenomas, which do not result in any abnormal hormone excretion. Other less common pituitary adenoma subtypes seen in FIPA include adrenocorticotropic hormone-secreting tumors (which cause Cushing disease), thyrotropinomas (TSH-secreting) and corticotropinomas (ACTH-secreting). Malignant transformation of PA in FIPA appears to be rare.
Individuals with a pathogenic variant in AIP have an increased risk of developing pituitary adenomas compared to the average person. AIP-associated FIPA appears to have reduced penetrance of 20%-66%; this means not everyone with such a variant will develop a pituitary adenoma (PA). Further, the same variant may manifest with different types of pituitary adenomas, even among family members. Because we cannot predict if an affected individual will develop a PA nor which type, additional medical management strategies focused on early detection may be beneficial.
The AIP gene accounts for ~15-30% of FIPA cases. Sequence analysis identifies ~90% of detectable variants and deletion/duplication analysis identifies ~10%.
FIPA is inherited in an autosomal dominant pattern with reduced penetrance.
Testing for AIP may be considered for individuals with a personal and/or family history of features, including:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|