18th century Irish giant helps find genetic cause of acromegaly
7 Jan 2011
An Anglo-German research team has analysed the genes of the
Irish Giant skeleton held in the Hunterian Museum in London to help
identify the genetic mutation responsible for acromegaly.
It is hoped that the discovery will help in the treatment of
patients suffering from acromegaly, which is also called gigantism.
Gigantism is known to be caused by a tumour of the pituitary
gland, a gland located at the base of the brain from where it
releases hormones that regulate several functions of the body — one
Pituitary tumours can cause tissues to grow abnormally resulting
in certain changes in facial appearance, enlarged hands and feet,
headache and sweating — eyesight too can be affected; this condition
is called acromegaly.
Márta Korbonits, Professor of Endocrinology and Metabolism at
Barts and the London School of Medicine and Dentistry, initially
looked at the aryl hydrocarbon receptor interacting protein (AIP)
It has been known since 2006 that defects to this gene are
associated with a predisposition to development of pituitary
tumours, and Professor Korbonits was able to identify a specific
genetic mutation in Irish patients with a family history of
Leading international paleogenetics experts Professor Dr Joachim
Burger and Martina Unterländer of the Institute of Anthropology at
Johannes Gutenberg University Mainz, Germany, subsequently extracted
and analyzed the DNA from the skeleton of an 18th-century acromegaly
patient preserved in the Hunterian Museum in London.
Analysis of old DNA at JGU labs. Photo credit:
The research team discovered exactly the same mutation as the one
found in living patients. Further analyses of other DNA segments
located in the vicinity of this gene led to the conclusion that the
Hunterian Museum's so-called "Irish Giant" had inherited the
mutation from a common ancestor that he shared with a number of
living Irish families who are suffering from this hereditary
The subsequent complex biostatistical calculations showed that
the original mutation developed around 1,500 years ago and has been
passed on from generation to generation ever since. It is estimated
that around 200 to 300 people still carry the mutation today.
"The ancient DNA from the skeleton has enabled us to confirm the
hypothesis that there is indeed a link between the mutation and this
disease, a disorder which in the past so often resulted in tragedy,"
explains Professor Joachim Burger from Mainz University. "The
biomathematical calculations have even provided us with a highly
accurate insight into the history of this illness."
Márta Korbonits, head of the study, adds: "The most important
clinical aspect of our study is that it is now possible to trace
down carriers of this gene in time and treat patients before they
grow to be a giant."
Professor Patrick Morrison, co-author of the study, concludes:
"He benefits to patients locally are that we now have a genetic
blood test that families at risk of this condition can choose to
have, which allows early detection and prevention of excessive
1. Chahal, HS, et al. AIP Mutation in an 18th
Century Giant and Contemporary Families with Pituitary Adenomas.
The New England Journal of Medicine 2011; 364:43-50 (6 Jan.