CRISPR’s quest to slay Donegal Amy

The northwest tip of the Irish coast was named after an Irish king in the 5th century. The land of Conall was referred to as Tr Chonall.

A mistake in a scion's genome is thought to have arisen in the line of the king's descendants. A rare condition called hereditary transthyretin amyloidosis was caused by the genetic error.

The TTR protein is made predominantly in the liver and is responsible for shuttling vitamin A and a hormone called thyroxine around the body. But in those with hereditary ATTR amyloidosis, the genetic mutation produces a botched version of it. This misshapen TTR aggregates and leaves clumps of amyloid, another protein, in tissues around the body—mostly the heart muscles and the nerves. These amyloid clumps interfere with tissues as they try to do their job, wreaking havoc.

About 1 percent of the population are found along a 15-mile strip of the coast of Donegal where the Irish language is still mostly spoken. For decades, Donegal natives have been ravaged by a disease called Donegal Amy.

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There are about 50,000 people with hereditary amyloidosis in the world. There are more than 130 genes that are thought to cause other forms of the condition. Hyperlocalized clusters are where carriers of these genes tend to show up. Val30Met can be found in northern Portugal, as well as in northern Sweden and Japan. About 4% of African Americans are estimated to carry Val122Ile.

In the case of Donegal Amy, the condition usually becomes known after 60 years of age. It starts with a sensation of weakness in the body's limbs, such as the hands and feet, and moves inwards, causing pins and needles and other symptoms. The disease attacks the autonomic nervous system, which regulates bodily processes, and causes weight loss and other symptoms. cardiomyopathy is a disease of the heart muscle that causes breathlessness, chest pain, and swelling of the legs, ankles, and feet. The symptoms of hereditary amyloidosis are so heterogeneous that doctors rarely know when they have a case. A patient wouldn't usually tell their doctor about carpal tunnel syndrome or a heart problem. Researchers have noted that the diagnostic pathway is rife with pitfalls.