DNA Mutation May Play a Role in Age at Which Familial Amyloid Polyneuropathy Starts, Study Reports

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by Magdalena Kegel |

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NTLA-2001, Gene Editing

The age at which symptoms of familial amyloid polyneuropathy (FAP) start showing up may be influenced by other genetic factors, according to a study that assessed genetic variation in a large number of patients.

Researchers at the University of Porto in Portugal hope their findings lead to researchers exploring treatment targets that can delay the age when the genetic nerve disease starts.

The study, “A Trans-acting Factor May Modify Age at Onset in Familial Amyloid Polyneuropathy ATTRV30M in Portugal,” appeared in the journal Molecular Neurobiology.

The most common mutation that causes FAP is what is known as the Val30Met substitution in the TTR gene. All patients with this type of FAP — also called ATTRV30M amyloidosis — carry the same mutation. But they tend to fall ill at very different ages. Even in the same family, there can be more than a decade’s difference in the start of the disease.

Researchers wanted to know if other genetic factors could play a role in the age at which those carrying a TTR mutation become ill. Their study covered 910 people — 589 mutation carriers, 102 spouses, and 189 controls from the general population.

The team homed in on eight small DNA mutations in the vicinity of the mutated TTR gene. Scientists call the DNA mutations SNPs. They tended to be transmitted from parent to child in various combinations, the researchers discovered.

Parents who did not carry an FAP mutation tended to pass on one SNP combination to their children, while the vast majority passed on another.

When researchers compared patients who had fallen ill before the age of 30 with those who developed the disease after 50, they discovered a link between one of the eight DNA mutations and the age when the disease started. 

The team acknowledged that they are still uncertain whether the DNA mutation actually impacts the age at which the TTR-triggered symptoms emerge, however.

That’s because of what scientists call linkage disequilibrium, or nearby stretches of DNA being inherited together. This means the DNA mutation could simply be close to other genetic material that affects the age when FPA starts.

The team called for more research that could give scientists a better understanding of the factors at play when the disease starts. This additional insight could lead to ways to delay the onset of the disease, they said.