Japanese Region Has Several Examples of Rare FAP Mutation, Case Study Reports

Patricia Inacio PhD avatar

by Patricia Inacio PhD |

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FAP and genetic testing

A rare mutation of a gene involved in late-onset familial amyloid polyneuropathy occurs at higher rates in one Japanese region, a case study reports.

The research, “Two cases of late onset familial amyloid polyneuropathy with a Glu61Lys transthyretin variant,” was published in the Journal of the Neurological Sciences.

Most cases of familial amyloid polyneuropathy (FAP) are caused by mutations of the TTR gene. The first one that scientists identified — the Val30Met mutation — is still the most common of the more than 100 linked to early onset of the disease.

Other mutations lead to less frequent manifestations of FAP, such as late-onset cases.

Japanese researchers discovered two cases of late-onset TTR-FAP in patients with the less common Glu61Lys mutation.

Neither the 77-year-old man nor 72-year-old woman, both of whom were from the Okayama region in southwestern Japan, had a family history of FAP.

Both experienced symptoms seen in previous research on three other Japanese. These included leg swelling, abnormal feelings in limbs — such as cold when it wasn’t cold — and weakness. The woman was also having trouble breathing.

The two patients were experiencing less common FAP symptoms as well. They included heart problems and mild dysfunction of the autonomic nervous system — the one that controls functions such as heartbeat and breathing.

“Such manifestations are sometimes similar to senile systemic amyloidosis,” the researchers wrote. The way to distinguish late-onset FAP from senile systemic amyloidosis is genetic testing, they said.

Two of the three other late-onset cases of FAP in Japan that appeared in previous research were also from the Okayama region. When the two recent cases were included, this meant that four of the five FAP cases that the research team was aware of were from the same region. None of the four was related, researchers said.

The findings suggested that being in Okayama was a common thread in the Glu61Lys mutation of the disease, the team wrote.

“Regarding the Glu61Lys TTR variant, focus should be on preceding restrictive cardiomyopathy, regional cases in Okayama (Japan), and other common clinical characteristics of late-onset TTR-FAP,” the researchers said.