Identification of this gene defect using DNA-chip technologies is an example how genetic research can tackle more and more demanding tasks, such as identification of predisposition genes conferring a low absolute but high relative risk. The results are published in the May 26 issue of the journal Science.
The research group, lead by professor Lauri Aaltonen (University of Helsinki, Finland) and Dr Outi Vierimaa (Oulu University Hospital, Finland) providing the initial observations leading to the investigations, aimed at unravelling the genetic basis of susceptibility to pituitary adenomas. Pituitary adenomas are common benign neoplasms, accounting for approximately 15 % of intracranial tumors.
Most common hormone-secreting pituitary tumor types oversecrete prolactin or growth hormone (GH), which together with local compressive effects account for their substantial morbidity. Oversecretion of GH causes acromegaly or gigantism. Acromegaly is characterized by coarse facial features, protruding jaw, and enlarged extremities. The potentially severe symptoms of untreated acromegaly, develop slowly and the condition is difficult to diagnose early. Gigantism refers to excessive linear growth occurring due to GH oversecretion when epiphyseal growth plates are still open, in childhood and adolescence. Genetic predisposition to pituitary tumors has been believed to be rare.
The researchers detected three clusters of familial pituitary adenoma in Northern Finland. Genealogy data reaching back to 1700’s was available. Two first clusters could be linked by genealogy. The researchers hypothesized that a previously uncharacterized form of low-penetrance pituitary adenoma predisposition (PAP) would contribute to the disease burden in the region. The researchers had previously characterized a population based cohort diagnosed with GH secreting pituitary adenoma (somatotropinoma) in Oulu University Hospital (OUH).
These data were linked to the pedigree information, to identify additional affected distant relatives. The PAP phenotype – very low penetrance susceptibility to somatotropinoma and prolactinoma - did not fit well to any of the known familial pituitary adenoma syndromes. These syndromes are defined by familial occurrence of the disease, and the low penetrance of PAP appeared unique. Low penetrance means hereditary predisposition which relatively rarely leads to actual disease – but which may cause much more effect on population level than high-penetrance disease susceptibility which typically is very uncommon.
Utilizing modern chip-based technologies the research group identified mutations in the AIP gene as the underlying cause. Further work on the functional role of this gene should prove informative in revealing key cellular processes involved in genesis of pituitary adenomas, including potential drug targets.
It has not been previously realized that genetic predisposition to pituitary adenoma, in particular GH oversecreting type, can account for a significant proportion of cases. The study not only reveals this aspect of the disease, but also provides molecular tools for efficient identification of predisposed individuals. Without pre-existing risk awareness, the patients are typically diagnosed after years of delay, leading to significant morbidity. Simple tools for efficient clinical follow-up of predisposed individuals are available, such as monitoring GH in blood samples.
In a general sense, the results suggest that inherited tumor susceptibility may be more common than previously thought. The identification of the PAP gene indicates that with the new DNA-chip based technologies it is possible to identify the causative genetic defects in the low-penetrance conditions even in the absence of a strong family history.
Paivi Lehtinen | alfa
Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System
Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea University
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
22.08.2017 | Health and Medicine
22.08.2017 | Materials Sciences
22.08.2017 | Life Sciences