Scientists at Ben-Gurion
University of the Negev, Israel, studied ten patients from four
families that have PCCA2 (Progressive Cerebello-Cerebral Atrophy Type 2).
Children who have the disease appear
normal at birth and develop as expected until about six months. However, by one
year, patients develop brain atrophy (a loss of brain cells), mental
retardation and epilepsy. At three years old, most patients will be in a
The work to find the gene behind the
condition was led by Professor Ohad Birk and Miora Feinstein, a doctoral student.
They found that the disease is caused by two different mutations in the same
gene - VPS53.
The exact reasons why
VPS53 mutations cause PCCA2 are unclear. However, the researchers that the tiny
pockets that carry material around cells, called endosomes, do not move around
like they should. As a result, waste material, which should
be broken down and destroyed, builds up within the cell.
Professor Birk's group has now discovered more than 20 genetic diseases found in people of Arab and Sephardi Jewish backgrounds. In 2010, they identified mutations in a gene called SESPSECS, which prevent the mineral selenium
from being used in the body and cause a very similar disease called PCCA.
'There was an idea that Ashkenazi
Jews have more disease than others, but when one begins looking at Sephardic Jewish
diseases, they are there', Professor Birk said.
'They have just not been sorted out.
Because they have not been sorted out, there was no carrier testing, no
prevention programmes or anything. I have shifted part of my lab into this,
into Jewish non-Ashkenazi - or Sephardic Jewish - diseases'.
PCCA2 is a recessive disease, meaning that both
parents must be carriers of a VPS53 mutation. Children have a 25 percent risk of inheriting two mutated copies of
VPS53, and having the disease.
As one in 37
Moroccan Jews carry VPS53 mutations, PCCA2 is now the most common severe genetic disease in this community.
Fifteen percent of Israel's population (one million people) is of Moroccan ancestry. Nearly 100,000 Moroccan Jews also live in the USA, meaning a large number of people are at risk of inheriting the disease.
Carrier testing for SESPSECS
mutations was introduced in 2011 for all Jews of Moroccan or Iraqi ancestry. Now researchers have called
for routine carrier screening for VSP53 mutations as well. This might even
start within the year, and could help reduce the number of people inheriting
The study was published in the the Journal of Medical Genetics.