Giant Gene Discovered
In 2006, Finnish researchers discovered that a mutation of the AIP gene located on chromosome 11 is responsible for gigantism in families in Finland. After that research, London-based clinician and researcher Prof. Márta Korbonits realized that a number of her patients with familial gigantism came from a small area in Northern Ireland. Her research determined that the Irish patients shared a specific variant of the AIP mutation, ARG304STOP codon. The area west of Lough Neagh in Co. Tyrone and Co. Derry is now considered to be a genetic hotspot for the disease. She then linked that mutation to a famous 18th century Irish giant who once lived in the genetic hotspot named Charles Byrne, whose skeleton is available in the Hunterian Museum in London, England.
The Traveling Gene
Dungannon resident, Brendan Holland has lived most of his life in the genetic hotspot identified in Prof. Korbonits’ research. He was treated in 1972 for gigantism at St. Bartholomew’s Hospital in London, and in 2010, he met Prof. Korbonits at the hospital during the filming of the documentary Charles Byrne, the Irish Giant. He is committed to furthering Dr. Korbonits’ research and identifying others with gigantism.
Diagnosed in 1976 in Washington, D.C. at age 20 with acromegalic gigantism, Colleen Snyder searched for 45 years to find another person with the same diagnosis. During the COVID lockdown in 2020, through serendipity, a Google search, and a at-home DNA test kit, she found out that the rare AIP ARG304STOP genetic mutation caused her gigantism. The mutation was brought over to the U.S. when her great-great-great grandfather emigrated from Coalisland, Co. Tyrone in the genetic hotspot in Northern Ireland. She is the first person in the United States identified with the mutation.
Colleen contacted Prof. Korbonits who introduced her via Zoom to Brendan. Despite living an ocean apart, Colleen and Brendan quickly joined forces to combat the potentially deadly disease. They share a common purpose: to educate others about the devastating effects of gigantism and how predictive genetics provides hope to prevent gigantism in the future.
Gigantism and Acromegaly
Gigantism (and its related disorder acromegaly) is not just about being tall. The disease is caused by a tumor or adenoma on the pituitary gland (located in the middle of the head behind the eyes) that starts to grow in childhood. The pituitary gland affects all the hormones in the body. Excessive growth hormone from the tumor causes the extreme height reached by some patients. There are many more symptoms, including vision loss, severe headaches, debilitating joint pain, and metabolic dysregulation. Left untreated, most patients die before the age of 30.
With the discovery of the AIP gene and the specific variant linked to Northern Ireland, it is certain that some of those immigrant families brought the AIP gene mutation with them. As of 2022, only one family has been identified with the Irish mutation in the U.S. Probability indicates there must be more families living outside of Northern Ireland, most likely in North America or Australasia. Our goal is to find those families and provide them with the information to prevent any family members from suffering the devastating effects of gigantism.
– Brendan Holland, Dungannon, Co. Tyrone, Northern Ireland
– Colleen Snyder, Linden, Virginia, USA
Community Testing
In 2013, Prof. Korbonits, her London team, and endocrinologists from Mexico, Romania, and Venezuela set up medical tents in Tesco car parks in Cookstown and Dungannon to gather more than 900 DNA samples from local residents in Co. Tyrone. The screening identified families with the same mutation and many family members with manifestations of the disease. Statistical analysis determined the founder of this particular mutation in Northern Ireland lived over 100 generations ago and could explain the many legends and folk tales about giants in Irish folklore.
Prof. Márta Korbonits, MD, PhD, Professor of Endocrinology and Metabolism, Queen Mary University of London and Barts Health NHS Trust, London, United Kingdom
Ronan McCloskey, producer and director, Charles Byrne: The Irish Giant
In 2010, Ronan McCloskey began filming the BBC documentary Charles Byrne: The Irish Giant, originally commissioned as a biography of the famed Irish giant who died in 1783. A native of Omagh in Northern Ireland, McCloskey knew of modern-day giant Brendan Holland and invited him to London to see Byrne’s skeleton during filming. When McCloskey contacted the Hunterian Museum where the giant’s skeleton had been displayed since his death, officials told him that researcher Prof. Korbonits had obtained Byrne’s DNA for comparison to contemporary Irish giants. When McCloskey arrived in London to see Byrne’s skeleton and meet Prof. Korbonits, it quickly became apparent that the documentary would be much more than a simple biography. McCloskey introduced Prof. Korbonits to Brendan who would play a pivotal role in Korbonits’ research, and he chronicled the story of Korbonits’ groundbreaking research AIP Mutation in Pituitary Adenomas in the 18th Century and Today published to acclaim in the New England Journal of Medicine in 2011.
St. Bartholomew’s Hospital, London, United Kingdom
Celebrating its 900th anniversary in 2023, St. Bartholomew’s Hospital or Barts has played a crucial role in the diagnosis of gigantism and the research detailing its cause. Established in 1123 by visionary monk Rahere, Barts has long engaged in cutting-edge research into the panorama of human diseases and conditions. In May 2022, Colleen traveled to Barts with her sister Cherie Moye, who is a carrier of the AIP gene, to meet Prof. Korbonits, her mentor renowned endocrinologist Prof. Mike Besser, and Dr. Ben Loughrey, a fellow in the genetics of pituitary adenomas. Brendan and his son Stephen made the journey as well. It was a homecoming for Brendan who was treated there, and an opportunity to learn more about the disease and related research. For example, studies continue on the effect of the AIP gene mutation on carriers. Not everyone who gets the AIP mutation from their parent goes on to develop the disease. It is unclear why the disease only occurs before the age of 25 and why only 25% of those who carry the defective gene develop the disease in childhood. At Prof. Korbonits’ laboratory in the Centre of Endocrinology at Queen Mary University of London, researchers contine to study the AIP gene and related genetic disorders.
Familal isolated pituitary adenoma (FIPA) is a pituitary tumor that is caused by a genetic mutation that runs in a family. The AIP ARG304STOP gene mutation that is found in Northern Ireland is one type of FIPA . There are others found throughout the world. There are also other gene mutations that cause gigantism. For more information about FIPA in general and more detailed information about the AIP mutation found in Northern Ireland, go to the Queen Mary University of London website https://www.qmul.ac.uk/fipa-patients/
CONTACT US
We are committed to reaching out and finding families affected by the AIP genetic mutation. We want to hear your story. We are also here to provide families and patients accurate and up-to-date information. You can contact Colleen Snyder at csnyder123@comcast.net or Brendan Holland at brendan@promaxequipment.com for more information.