Identify the causative gene mutation of gigantism from the DNA of the legendary "Irish giant", skeletal specimen of the 18th century

Northern Ireland·DungannonMr. Brendan Holland living in the country has a long body of 6 feet 9 inches (about 206 cm). I began to grow tall explosively at the age of 13,Pituitary glandBy tumorGrowth hormoneIs over-secretedAcromegaly(Pituitary gigantism), it seems that treatment is received at the age of 20 and the growth of height has stopped, but both parents and brothers are average height so "why myself so much taller It seems that he had been wondering forever.

RecentlyBarts and The London School of Medicine and Dentistry, The four families of modern Northern Ireland including Mr. Holland are famous in the 18th century called "Irish giant"GigantismPeopleCharles BurnIt was found to be distantly related, and common genetic mutation was identified.

Details are as below.The Body Odd - Real-life Irish giants traced to 18th century street performer

Charles Byrne (1761 - 83)

Born in southern Ireland in 1761, Charles Burn crossed the mainland of Britain to make the tallest beyond 8 feet (about 243 cm, thought to be 231 cm in the postmortem examination by skeletal specimens), and festivals in Scotland and northern England After appearing as "Giant" in etc., arrived in London in 1782Sightseeing hutWhen it entered, explosive popularity was taken and we gained wealth and fame overnight.


However, the popularity did not last long but was immediately replaced by another spectacle, losing property due to a failure of investment, in June, 1783, died at young age 22 by excessive drinking. Although he did not have a will, Baan, who was afraid of "becoming an anatomist's toy" after death, said he asked his friends that "I want you to put it in the lead and put it in the ocean." As he wished, after the death of Baan, the shepherd was thrown into the sea, but in fact this sheep was empty and the body of Baan was taken by a surgeon / anatomist by the funeral man who received the bribeJohn HunterIt was sold to.

John Hunter who is called "father of experimental medicine" or "founder of modern foreign science" and contributed to the development of modern medicine is an illegitimacy of procurement of corpse for anatomy classroom and procurement route of animal specimen, brother A gynecologistWilliam HunterSuch as involvement with an incident that killed a large number of pregnant women because of dissection, people who have dark side.Joshua ReynoldsThe portrait of the Hunter by the legs of Charles Burn's skeletal specimen is drawn.


When obtaining the corpse of Bahn, the hunter who was afraid of discovering it, it instantly chopped into a size to cut into a pot, boiled and left as a specimen leaving only the skeleton, and it was confirmed that the body was acquired only after four years since the death of Baan It is said that.

Currently this specimenThe Royal Surgical Medical Association of EnglandofHunterian MuseumIt is on display in.


We studied this skeletal specimen of Charles Burn in 1909Harvey Williams Cushing(Cushing's disease, An American neurosurgeon), the bone just under the pituitaryTurkish saddleBecause it is hypertrophic, in BaanPituitary adenomaI judged that there was.

Barts and the London School of Medicine (University of LondonDr. Marta Korbonits, a professor of metabolism and endocrinology at the Queen Mary College medical school) and others examined the DNA obtained from specimens of Barn's teeth,AIP gene(Aromatic hydrocarbon acceptorA gene that encodes a protein that binds to a germline mutation). Thesis isNew England Journal of MedicineIt is published in the magazine. Also in the current Northern IrelandAcromegalyOrProlactinoma(ProlactinFour families reported that mutations of this AIP gene are common, and the merging point of the two families (at the time when the most recent common ancestor existed) was statistically analyzed by a method of statistical analysis presume"Coalescent theory(Consolidation theory) ", it is estimated that there was a common ancestor from the 57th generation to the 66th generation before (1425-1650 years ago).

Professor Marta Korbonits who sees the skeletal specimen of Charles Barn, and Brendan Holland, one of the four families who cooperated in research.


Mr. Holland, now in his 50's and a height of 6 feet 9 inches (about 206 cm), began to grow in height rapidly at the age of 13, saying, "I am always tired and suffering from a bad headache,Tunnel view(Narrowing of the visual field). It turned out that growth hormone was excessively secreted by pituitary adenoma, and when he was treated at the age of 20, he had stopped growing his height, but he said that if he left it, he would have further increased. After that, Mr. Holland seems to have learned that the locality is an area known as "hotspot of pituitary adenoma" among scientists.

Although Mr. Holland says that both parents and brothers were wondering because they are average height, it seems that it was somewhat clearer to understand that it was "a family of gigantism" with a common ancestor to "Irish giants". But for Mr. Holland, who has two sons, it is more important to serve the future descendants than I knew about my past fathers with this discovery. "My child and grandchildren can check if they have this mutation, and if it turns out to be gigantism, it will be possible to treat early from the height before the height starts to explode. "Said Holland.

Professor Marta Korbonits, who is hoping that this finding will lead to a further understanding of pituitary adenoma, says, "These people are ordinary people with sickness, not inflexible or freaks, It is people who genetically attract the risk of gigantism as well as genetically attracting the risks of diseases such as disease and diabetes from their parents. "