Identification of the genetic basis of mental retardation in affected Israeli and Palestinian families and development of preventive program.


Dr. R. Sharkia

Dr. A. Azem


Introduction and Background: 

Many genetic diseases are rare in the general population, but become unusually frequent in certain communities worldwide due to genetic isolation that originate from various social, geographic and religious factors. The most prominent social behavior that leads to higher rates of genetic disorders is consanguinity (Zlotogora, 1997). The phenomenon of consanguineous marriages was common in different societies worldwide since many decades. The prevalence of consanguineous marriages in the Arab world is considered to be very high (35% - 55%) in comparison to that (~1%) in the Western countries (Bittles et al. 2001). Recently, different studies about various Arab societies have shown that consanguinity rates decreased with time (Hamamy et al. 2005, Sharkia et al. in Press). The relationship between consanguineous marriages, inherited genetic diseases and congenital malformation was examined in many studies since many decades. It was found that consanguineous marriages were a major cause of high rate of congenital malformation and neonatal mortality among Israeli Arab community (Jaber, 1992, Zlotogora, 1997). Furthermore, consanguineous marriages among Palestinian population were related with high rate of infant mortality (Pedersen, 2002). One study that focused on the β-globin gene mutations among Palestinian Thalassemia patients in the West Bank region was homozygous for one mutation and that 76% of their parents were first cousins (Darwish et al, 2005).

   Mental retardation (MR) is a frequently occurring disease with a major impact on the life of affected person, the family and society. MR is defined as a disability characterized by a remarkably low intellectual functioning (IQ<70) in conjunction with significant limitations in adaptive functioning (American Association on Mental Retardation). The estimated prevalence of MR is 1-3% of the general population (Mclaren and Bryson, 1987). A report published by Abu-Rabia and Maroun (2005) showed that consanguinity negatively affects the children's reading ability. The genetic aetiologies of MR are diverse and include chromosomal anomalies, recognizable malformation syndromes, monogenic syndromes, structural brain abnormalities and environmental factors.  About 1,400 different conditions associated with mental retardation has been recognized to date (London Dysmorphology Database), and many more are yet to be characterized, making the clinical or the genetic diagnosis extremely challenging. Clinical observations and the study of large families with MR males have highlighted the importance of genes located on the X chromosome. The collective efforts of many research scientists have led to the identification of 59 genes that are associated with syndromic and non-syndromic X-linked mental retardation (Ropers and Hamel, 2005). The X-linked mental retardation may account for about 15-25% of mentally retarded males (Kleefstra and Hamel, 2005).  On the other hand, only two autosomal genes had been shown to cause autosomal recessive NSMR (Basel-Vanagaite et al. 2005), and more than 50% of MR cases remain undiagnosed (Santos et al. 2006).

In certain societies characterized by high frequencies of certain genetic disorders, various activities and programs had been undertaken; for example the one for prevention of Tay Sach's disease among the Jewish population in Israel. In various communities of the Mediterranean region, genetic screening of Thalassemia has been performed, since this genetic disorder is prevalent in high frequency in this region (Hoedemaekers and Have, 1998, Koren et al. 2002), proving to reduce the rate of the screened disorder among the population. 

This proposed research work is focused at mental retardation, which is a severe, incurable and also discriminative disorder, in order to develop tools to reduce its prevalence in a defined population. This approach is vital for improving health care through the surveillance of the spectrum of MR diseases as well as through identifying and diagnosing their molecular genetic basis and their prevalence in selected communities of Arab population in Israel and in the Palestinian authorities, which occasionally share common ancestors. Furthermore, it is crucial in order to implement preventive programs and design future strategies leading to minimizing the occurrence of these inherited genetic disorders. The joint venture between the German-Israeli-Palestinian scientists will be the main asset to carry out this humanitarian-health related research work.