Mutations in genes responsible for two serious neurological disorders in infants
and children of Iranian and Bukharan origin that had not been described until
now have been identified by researchers at Sheba Medical Center at Tel Hashomer,
the Weizmann Institute of Science in Rehovot and Duke University in North
Their work has just been published in the prestigious journal
Neuron and the American Journal of Human Genetics.
The mutations were
identified as part of research project to locate the genetic causes of some 100
serious diseases in the Israel population that have not been clear despite
significant efforts to find the answers.
The work involved cooperation
among Prof. Bruria Ben Zeev (head of the pediatric neurology unit at the Edmond
and Lily Safra Children’s Hospital at Sheba; Prof. Yair Anikster (head of
Safra’s metabolic disease unit); Prof. Alon Peres (head of Safra’s
genetic institute); Prof. Doron Lancet (head of Weizmann’s Center for Genome
Research); and Prof. David Goldstein (head of the Duke Center for Human Genome
Changes in the first gene causes a rare type of microcephaly
(a small brain) in children of Iranian Jewish origin; they were under
observation for years at Safra and at the neurology unit at Wolfson Medical
Center in Holon.
The symptoms include having a head with a smaller-than-usual circumference at birth, slow growth of the head afterwards, severe mental
retardation and convulsions.
The defect affects boys and girls equally
and causes severe disability throughout their lives.
discovered that the gene is coded for the protein enzyme called asparagine
synthetase (ASNS), which is responsible for the production of the amino acid
called aspergine. This substance is one of 20 building blocks of all proteins
and is provided in food, but because of the mutation, there is a major decline
in its concentration in the brain. This harms brain development in the fetus at
its early stages and causes accumulated damage after birth.
it is a metabolic disease, the usual metabolic tests do not identify the defect
because the measured levels of enzymes do not significantly vary from the normal
range. Thus the new knowledge makes possible a specific genetic test for the
The carrier rate among Jews of Iranian origin is high and reaches
one per 60. Discovering the gene will make it possible to identify carriers of
the disease before pregnancy, and the diagnosis of other patients. The
researchers are looking into the possibility of developing treatment
interventions for cases in which the mutation is not identified before
The second mutation causing a genetic disease was found in
children of Bukharan Jewish origin treated at Safra’s neurology unit. The
carrier rate in this ethnic group is high – 1 per 40. This mutation causes
severe retardation and muscle problem and often prevents children from walking
Such children sometimes develop epilepsy and have
respiratory troubles, especially during sleep, requiring respiration over night.
The gene is called TECPR2 and involves the breakdown of various waste products
in the body, including the brain. This process is called autophagy.
present, there is no treatment, but the discovery will allow the identification
of carriers and affected fetuses.
The cooperation between Israelis and
researchers abroad makes it possible to prevent such severe genetic diseases
from being handed down to offspring and will help find ways to treatment these
and other disorders, the researchers said.