  How Scientists Identified The Mutant Gene That Was Devastating A Bedouin Community by Sarah Meyer From The Jerusalem Report, May 6, 2002 FOR YEARS, SALAMA, A Galilee village of neat cinderblock homes inhabited by 3,000 Bedouin, was blighted by recurring tragedy. The way Hasan Suwa’ed tells it, sipping mint tea and reclining on a cushion in the tent outside his house where he receives guests, at least nine Salama children died inexplicably in a period of just eight years—leaving parents devastated and doctors baffled. Suwa’ed lost his own 5-year-old son, Hossan, in 1994. Two of his uncle Zeidan’s eight children died too. And many other young kin among the Suwa’ed tribe of Salama, which sits on a mountainside near Karmiel, had frequent fainting spells and unexplained weakness. Attempts to treat the Salama malady as epilepsy or some form of Parkinson’s disease were unsuccessful, and parents despaired over ever solving the deadly mystery. But then, four years ago, Zeidan took his oldest daughter, 14 at the time, to Sheba Medical Center at Tel Hashomer near Tel Aviv. She was showing the terrifying trademark symptoms, and was diagnosed as suffering polymorphic ventricular tachycardia (PVT), an irregular heartbeat that, if left untreated, as her parents knew only too well, is often fatal. Diagnosing PVT, a relatively rare ailment, is itself a risky business: the best way to confirm the malady is via a stress test, on a treadmill. Sheba wanted to ascertain whether this was the illness afflicting the village of Salama—but stress testing could put the young patients at risk by causing severe palpations. Sheba’s chief cardiologist, Micha Eldar, turned to one of his own students, Hadas Lahat. Lahat, working toward a PhD in genetics, visited Salama and, with the most careful use of stress tests, found 13 children with PVT. She then began collecting blood from a wider sampling of villagers. All the evidence pointed to a genetic problem. But the faulty gene had to be identified. After taking blood samples from everyone in the village, she identified a problem on chromosome 1, which meant that there were about 100 suspect genes. To narrow the search, she turned to the Weizmann Institute’s Genome Center, which has the sophisticated equipment needed for advanced genetic research. The investigation could have taken years, but in a search through genetic literature, the Weizmann team found Italian researchers had isolated a gene that uses a similar disease. That helped speed the Weizmann scientists toward locating a mutation in the gene known as calsequestrin 2 (CASQ2), which plays a key role in the contraction and relaxation of heart muscles. The mutation, confirmed last year, impairs the ability of the CASQ2 protein to release calcium ions. “We got lucky, “acknowledges Weizmann team member Dr. Nili Avidan. “We solved the problem in one year. It could have taken much longer. So much for diagnosis; treatment is another story. The affected 13 Salama children—including Hasan Suwa’ed’s two other sons and three more of uncle Zeidan’s offspring—are being treated with the beta-blockers, a class of drugs that slow and regulate the heartbeat. Prenatal testing, now available in the village to all who request it, enables the proper drugs to be started immediately upon birth. These drugs are effective for 85-90 percent, but the physical activity of the young patients remains restricted. “They may be healthy, but they are not always able to act like children,” says Avidan. For example, Hasan Suwa’ed won’t let his two sons go to gym class. Hopefully, says Lahat, new medications to improve the children’s quality of life may now be developed. THEIR FATAL MYSTERY SOLVED, and the treatment made available, the villagers of Salama are now having to reevaluate a very basic aspect of their lifestyles—the Bedouin tradition of marrying close relatives. Lahat has warned them that the risk of the mutant gene, which is recessive, showing up “is much greater in any inbred family than in the general population.” That may be an understatement. In eight families with PVT victims, all of the parents were first or second cousins. Hasan Suwa’ed, married to his first cousin, estimates that there are “over 100” first-cousin marriages in Salama—including uncle Zeidan and his wife. He says that he won’t let his children marry a close relative, and that “recently we have started to develop and open up. And we try to marry outside the village.” Yet he acknowledges that the village “mentality is still that cousins marry cousins.” Suwa’ed has become something of a missionary for genetic testing in the village, insisting that, “If someone wants to marry a relative, they should do a genetic test beforehand. And if they are not OK, don’t get married—because the parents and children will suffer.” Of course, few know that better than he does. Without the researchers’ intervention, he said, “I might have no sons. My wife and I didn’t know about the tests. But there’s no reason for anyone else to go through what we’ve been through. © The Jerusalem Report, 1999-2001
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