Genetic Disorders in the United Arab Emirates: A 2006 Update

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1 G E N E T I C D I S O R D E R S I N T H E A R A B W O R L D - B A H R A I N Chapter 2 Genetic Disorders in the United Arab Emirates: A 2006 Update Ghazi Omar Tadmouri, Sarah Al-Haj Ali, Pratibha Nair, Abeer Fareed Centre for Arab Genomic Studies, Dubai, United Arab Emirates Introduction The initiative of the Centre for Arab Genomic Studies to establish a database for genetic disorders in the Arab World started in 2004 with a pilot project to catalogue genetic disorders in the Arab population of the United Arab Emirates. The strategy applied for this purpose consisted of data collection from a variety of sources including international and national bibliographic indices, nationally peer-reviewed medical journals, hospital records, and personal contacts (Tadmouri et al., 2004; see also Chapter 1). The efficacy of this strategy is clearly shown in the number of records collected in the database when compared to classical reviews on the subject (Al-Gazali et al., 1995; Abou-Chaaban et al., 1997; Al Talabani et al., 1998; Al Hosani and Czeizel, 2000; Al-Gazali et al., 2003). Genetic Disorders in the Arab Population of the United Arab Emirates As of October 2006, the CTGA database indicates the presence of 228 disease entries in the Arab population of the United Arab Emirates (Table 2.1). Data on only about 28 related genes are available in the CTGA database (Table 2.2). In conclusion, nearly 12% of all studies published on genetic disorders in the United Arab Emirates include investigations on the molecular basis of disease. This is far below the average of 35% recorded overall in medical research in the Arab World (Chapter 1). It is also an important indication that despite all progress achieved in the healthcare system in the country, more investment is required to establish reference centers aimed at depicting the molecular basis of genetic diseases in the country considering the cultural preference for consanguineous marriage and the presence of a rapidly expanding population. Ultimately, the identification of genetic lesions underlying many of these disorders would represent the necessary ground for the provision of screening and genetic counseling and, hence, to reduce the incidence of live births with these disorders in the country. Classification of Genetic Disorders in the United Arab Emirates Similar to the overall situation in the Arab World, congenital malformations and chromosomal abnormalities form the overwhelming majority of genetic Table 2.1. Alphabetical listing of genetic disorders in the Arab population of the United Arab Emirates as indexed in the CTGA database (October, 2006). 42

2 G e n e t i c D i s o r d e r s i n t h e U A E : A U p d a t e OMIM NAME 43

3 G E N E T I C D I S O R D E R S I N T H E A R A B W O R L D - B A H R A I N OMIM NAME 44

4 G e n e t i c D i s o r d e r s i n t h e U A E : A U p d a t e OMIM NAME 45

5 G E N E T I C D I S O R D E R S I N T H E A R A B W O R L D - B A H R A I N disorders in the United Arab Emirates, though at higher rate (Figure 2.1). A plausible explanation for this observation is the presence of several clinical genetic units at university, government, or private hospitals that made considerable contributions to the medical literature (Al- Gazali et al., 1995; Al Talabani et al., 1998; Al Hosani and Czeizel, 2000; Al-Gazali et al., 2003). On the other hand, disorders of the nervous system, the eye and adnexa, and the ear and mastoid process are below the overall Arab average probably because of the lack of enough expertise in the country or the interest to publish medical or genetic observations on these subjects. Molecular Complexity of Genetic Disorders in the United Arab Emirates In accordance with the dominant pattern in Arab populations, most of the genetic disorders observed in the Arab population of the United Arab Emirates are usually caused by mutations in single genes or gene loci (Figure 2.2). Less than 20% of genetic disorders in the country are of complex types and could be caused by abnormalities in one or several genes or gene loci. On the other hand, autosomal recessive genetic disorders represent an overwhelming proportion of all genetic traits in Arab patients in the United Arab Emirates (Figure 2.3). The increase in the rates of consanguineous marriages in the country is probably a major contributor to this observation. In fact, consanguinity rate in the United Arab Emirates has increased from 39% to 50.5% from the last generation despite the improvements in education, general economic conditions and health status of the population (Al-Gazali et al., 1997). The level of consanguinity is higher in Al-Ain (54.2%) than in Dubai (39.9%; Table 2.2. Alphabetical listing of gene loci studied in Arab individuals from the United Arab Emirates as indexed in the CTGA database (October, 2006). 46

6 G e n e t i c D i s o r d e r s i n t h e U A E : A U p d a t e Figure 2.1. Classification of genetic disorders in the Arab population of the United Arab Emirates and the rest of the Arab World using the WHO ICD-10 system (October 2006). Figure 2.2. Distribution of genetic disorders in the Arab population of the United Arab Emirates and the rest of the Arab World according to the number of causative gene loci (October 2006). Figure 2.3. Classification of genetic disorders in the Arab population of the United Arab Emirates and the rest of the Arab World according to mode of inheritance (October 2006). 47

7 GENETIC DISORDERS IN THE ARAB WORLD - BAHRAIN Table 2.3. Rates per 10,000 births of cases with congenital abnormalities and genetic disorders in the United Arab Emirates as constructed from the CTGA database (October, 2006). DISEASE 48 RATE REFERENCES

8 G e n e t i c D i s o r d e r s i n t h e U A E : A U p d a t e DISEASE RATE REFERENCES Al-Gazali et al., 1997) and Abu Dhabi (32%; Al Talabani et al., 1998). Overall, the most common pattern of consanguineous marriages has been and still is first cousin marriages (26.2% of all consanguineous marriages; Al-Gazali et al., 1997). Epidemiology of Genetic Disorders in the United Arab Emirates Until the public release of the CTGA database in 2004, a main obstacle that faced any genetic research in the UAE was the dearth of comprehensive statistical data on genetic diseases and their prevalence rates. This fate is changing forever with the dissemination of the knowledge accumulated in the CTGA database in the local, regional, and international scientific societies. The data shown in Table 2.3 demonstrates one possible example in which a user may benefit from the friendly interface of the CTGA database search engine to mine information on the birth rates associated with a number of genetic disorders and congenital abnormalities in the United Arab Emirates. Such information is imperative for any future applications to conduct newborn screening or implement diagnostic procedures and, hence, allow the content of the database to translate into practical applications. Current Directions in the Field of Genetics in the United Arab Emirates Besides the CTGA database, the Centre for Arab Genomic Studies undertook a significant step by organizing the First Pan Arab Human Genetics Conference in April The conference was the first of its kind in the region to present a platform for geneticists from all over the Arab world to exchange experiences and perspectives. An important landmark of the conference was the representation of the Human Genome Organization at a high level indicating the importance given by the international scientific community to the subject of human heredity in the Arab World. In a major attempt to initiate studies at the molecular level in the country, scientists at the Centre for Arab Genomic Studies 49

9 G E N E T I C D I S O R D E R S I N T H E A R A B W O R L D - B A H R A I N embarked on the identification of a large consanguineous kindred affected by ectrodactyly of the long bones for eight generations. The pedigree consisted of 145 individuals including 23 affected (14 males and 9 females) with limb anomalies. Possible candidate gene loci were identified through a genetic linkage study in the kindred. At present, work is ongoing to pinpoint the causative gene and probably understand the molecular mechanism leading to this complex genetic disorder (Naveed et al., 2006). Elsewhere, most recent genetic research in the United Arab Emirates has taken place on the hemoglobinopathies and cardiovascular disorders considering the high prevalence of both types of disorders in the country (Table 2.3). A recent study demonstrated that incidences of beta thalassemia and sickle cell anemia in the UAE show an increasing trend. Aditionally, 50 different mutations causing beta thalassemia have been identified in the UAE population, making it one of the most heterogenous populations in the world (Baysal, 2005). On the other hand, the numerous research works undertaken on hypertension serve to emphasize the wide-spread prevalence of this condition among the native population. These studies showed that family history of heart disease was a significant risk for developing hypertension, and more interestingly, that under-diagnosis and under-treatment of hypertension is common in the country (Sabri et al., 2004; Abdulle et al., 2006). The birth prevalence of total congenital abnormalities in the United Arab Emirates is calculated at 3% (Al Hosani and Czeizel, 2000) and approximately 42% of all neonatal deaths in the country do have congenital anomalies, most of which are genetic in nature (Dawodu et al., 2005). Recent studies have further stressed the fact that parental consanguinity is persistently associated with an increased risk of autosomal recessive disorders in the United Arab Emirates (Al-Gazali et al., 1997; Dawodu et al., 2005). However, the importance of genetic screening and counselling is still underscored in this rapidly developing country (Table 2.4) and strategies to reduce mortality rates due to inherited abnormalities are yet at their infancy. The success of these applications depends largely on the public perception of the genetic contribution to human health. In a recent survey to assess the level of understanding of genetic advice and attitudes toward consanguineous marriages and prenatal and preconception diagnoses, many investigated couples acknowledged a genetic basis for their child s condition (Al-Gazali, 2005). Furthermore, a majority agreed with carrier screening and preconception diagnosis in affected families. This acceptance is an important prerequisite for any possible subsequent preventive program. Worthmentioning is the Emirates Free of Thalassemia Project, which aims at reducing the impact of thalassemia and other haemoglobin disorders in the country. The suggested approach includes the conduction of a nation-wide screening program along with offering genetic counselling to people at risk. A somewhat similar program involving neonatal screening for sickle cell disease was initiated in 2002 in the Emirate of Abu Dhabi (Al Hosani et al., 2005). Results of this pilot program also advocated universal neonatal screening for sickle cell disease encompassing the entire nation. Interestingly, as an aside, an ambitious comprehensive nation-wide newborn screening and early intervention program is in the pipeline. Given the name Takamul, this initiative is supported by the Dubai Education Council with the major aims of establishing an early assessment and diagnosis centre and providing technical assistance to hospitals to boost their capabilities of early diagnosis of birth 50

10 G e n e t i c D i s o r d e r s i n t h e U A E : A U p d a t e defects and development delays. In the long term there no substitute for the training of sufficient individuals to service this need. In a recent review from neighbouring Saudi Arabia, short intensive training programs are proposed for graduates of medical sciences to create a generation of genetic educators who would work under the supervision of qualified professionals and provide basic counselling (Meyer, 2005). 51

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