gene mutation: 'Rare gene mutation that lowers sensitivity to pain found'

LONDON: Researchers have identified a rare gene mutation that may lead to low
sensitivity to pain, an advance that could help find new treatments for chronic
pain.
A team led by researchers at University College London (UCL) in the UK identified
the mutation that causes an Italian family, which includes six people, to have
unusually low sensitivity to pain.

"The members of this family can burn themselves or experience pain-free bone
fractures without feeling any pain. But they have a normal intraepidermal nerve
fibre density, which means their nerves are all there, they are just not working
how they should be," said James Cox from UCL.

The team found a novel point mutation in the ZFHX2 gene on conducting whole exome
sequencing- mapping out the protein coding genes in the genome of each family
member by using the DNA from blood samples.

The mutation alters a part of the gene's protein sequence that is normally
consistent across species as variable as mice and frogs.

"We are working to gain a better understanding of exactly why they do not feel much
pain, to see if that could help us find new pain relief treatments," said Cox, lead
author of the study published in the journal Brain.

Though one in ten people experience moderately to severely debilitating chronic

pain yet apart from common painkillers other treatments remain elusive, researchers
said.

One of the main areas of the research is to understand the cause of congenital
analgesia (inherited ability to feel reduced physical pain) which can lead to new
pain relief therapies.

The research team added to their previous work with the Marsilis family to explain
the nature of their phenotype (the visible characteristics caused by their
genetics) - named the Marsilis syndrome after the family's surname- finding that
they are hyposensitive to heat, capsaicin (found in chilli peppers) and have
experienced painless bone-fractures.
"By identifying this mutation and clarifying that it contributes to the family's
pain insensitivity, we have opened up a whole new route to drug discovery for pain
relief," said Professor Anna Maria Aloisi from University of Siena in Italy.
The researchers then conducted two animal studies to understand how the gene
affects pain sensations in mice.
They initially used mice that had been bred with the ZFHX2 gene entirely absent,
and found them to have altered pain thresholds.