Assaf Harofeh discovers mutant human gene that causes muscle weakness in Beduin babies

"Children who inherited the disease from their parents - healthy carriers who are first cousins - get better at around 14 and 15."

By JUDY SIEGEL-ITZKOVICH
Prof. Orit Reish 370 (photo credit: Courtes of Prof. Orit Reish)
Prof. Orit Reish 370
(photo credit: Courtes of Prof. Orit Reish)
A genetic mutation that has caused serious muscle weakness of 13 Beduin children from four families was discovered at Assaf Harofeh Medical Center in Tzrifin.
The advance that will help not only such inbred families but also explains the mechanism of muscle weakness in more common conditions.
It was the first time this gene was found in humans; in 2005, the gene was identified in golden retrievers, but caused a different disease in dogs.
Prof. Orit Reish, head of the genetics institute at the hospital, told The Jerusalem Post on Sunday that the “founder” of the autosomal recessive genetic defect lived about 50 years ago and was responsible for the “orphan” disease, which affects only a small number of people. A multi-institute and multidisciplinary medical team from Israel, the US and Japan worked for several years on discovering the mutant human gene, whose discovery was just published in the online, open-access edition of the journal Human Molecular Genetics.
“The discovery will help the families themselves, because we have learned that children who inherited the disease from their parents – healthy carriers who are first cousins – get better at around 14 and 15,” Reish said. “Soon after they’re born, their muscles are so weak that they often have to have a feeding tube inserted into their stomachs. The disease is not fatal. The children have difficulty breastfeeding and motor problems, cry weakly and suffer from respiratory problems and difficulty walking, but their cognitive abilities remain normal.
“Later, as teenagers, they are often able to walk, even if they fall down sometimes. The reason for the improvement is that other proteins that the children do have makes up for a protein important in childhood that is missing due to the defective HADC1 gene.”
The gene is not connected to the X or Y sex chromosomes and thus is equally found in boys and girls.
A major benefit from the discovery is that from now on, the disease can be identified in children who undergo a saliva or blood test; they will not have to go through a MRI or invasive, painful or expensive tests to be sure. In addition, parents can be assured that their condition will gradually become better. “Some of the patients are even over 30 years old,” said Reish.
Parent carriers can also undergo genetic counseling and decide on their own if they want to abort an affected fetus. Carriers can also undergo in-vitro fertilization and pre-implantation genetic diagnosis to ensure that the embryo implanted in the uterus is not affected by the defect.
“There is no treatment as of yet, but the discovery means that mechanisms that cause other diseases of congenital myopathy [muscle weakness] that affect larger populations are understood, and effective medications could be discovered,” the Tzrifin geneticist noted.
In numerous US states, Reish said, consanguineous marriage is not permitted so as to prevent first cousins from marrying and having a higher chance of giving birth to genetically defective children.
In Israel, families are discouraged from allowing first cousins to marry, but it is not prohibited. “I think, however, that inbreeding in the Beduin community is on the decline as they begin to marry outside their immediate environment,” she added.
“We have informed the Health Ministry about the gene and which community is affected, and those suspected of having the disease were sent to us for study,” Reish said.
Other researchers involved in the discovery included Prof. Ruti Parvari and Dr. Emad Muhammad of Ben-Gurion University and Prof. Val C. Sheffield of the University of Iowa; others came from the Hadassah University Medical Center in Jerusalem and from Japan.