High Rate Of Consanguinity Research Articles

Influence of socioeconomic lifestyle factors and genetic polymorphism on type 2 diabetes occurrences among Tunisian Arab and Berber groups of Djerba Island

Type 2 diabetes mellitus (T2DM) is characterized by three major metabolic abnormalities: impaired insulin-stimulated glucose uptake in muscle and adipose tissues, alterations in glucose-stimulated insulin secretion, and increased hepatic glucose production. Both genetic and environmental factors contribute to its development. The insulin gene (INS), insulin receptor gene (INSR), and insulin receptor substrate 1 gene (IRS1), identified by polymerase chain reaction and digestion with selected restriction enzymes PstI, NsiI, and BstnI, have been proposed as T2DM candidate genes. To determine the contribution of genetic and environmental factors on the occurrence of T2DM, we examined the frequency of T2DM among two ethnically diverse populations, Arabs and Berbers, who have shared the same environment, the island of Djerba, for thousands of years. Both populations have a high prevalence of obesity,T2DM, and a high consanguinity rate. A total of 162 T2DM men and women were matched to 110 healthy male and female controls. Results showed that the NsiI polymorphism in INSR and BstnI polymorphism of IRS1 were significantly associated with T2DM only among the Berber group. The PstI polymorphism in INS, was not associated with T2DM in either group. Sedentary lifestyles, lower physical activity, and lower educational levels were associated with T2DM among the Berber group. These findings suggest that the insulin receptor gene and lifestyle factors in combination may contribute to the occurrence of T2DM in the Berber portion of this island population.

CONSANGUINEOUS MARRIAGES IN MOROCCO AND THE CONSEQUENCE FOR THE INCIDENCE OF AUTOSOMAL RECESSIVE DISORDERS

Consanguineous marriage is traditionally common throughout Arab countries. This leads to an increased birth prevalence of infants with recessive disorders, congenital malformations, morbidity and mortality. The aim of this study was to evaluate the rate of consanguineous marriage in families with autosomal recessive diseases, and to compare it with the average rate of consanguinity in the Moroccan population. The study was conducted in the Department of Medical Genetics in Rabat on 176 families with autosomal recessive diseases diagnosed and confirmed by clinical, radiological, enzymatic or molecular investigations. The rate of consanguinity was also studied in 852 families who had infants with trisomy 21 confirmed by karyotyping. These families were chosen because: (i) there is no association between trisomy 21 and consanguinity, (ii) these cases are referred from different regions of Morocco and (iii) they concern all social statuses. Among 176 families with autosomal recessive disorders, consanguineous marriages comprised 59.09% of all marriages. The prevalence of consanguinity in Morocco was found to be 15.25% with a mean inbreeding coefficient of 0.0065. The differences in the rates of consanguineous marriages were highly significant when comparing the general population and couples with offspring affected by autosomal recessive conditions. These results place Morocco among the countries in the world with high rates of consanguinity. Autosomal recessive disorders are strongly associated with consanguinity. This study better defines the health risks associated with consanguinity for the development of genetic educational guidelines targeted at the public and the health sector.

Candidate Genes and Cerebral Palsy: A Population-Based Study

Interference with delivery of oxygen to the fetus or infant and other environmental risk factors have been associated with the development of cerebral palsy (CP). Several lines of evidence suggest that genetic risk factors are also involved; genes associated with vascular disease or inflammation, the fetal inflammatory response, and the apolipoprotein E genotype are all associated with increased susceptibility to CP. In addition, increased risk of CP has been demonstrated among groups with high rates of consanguinity and in certain families. This population-based study evaluated the association of selected genetic polymorphisms with later-diagnosed CP among 413 South Australian children born to Caucasian mothers between 1986 and 1999. Blood samples obtained from newborn screening blood spots were tested for 28 single-nucleotide polymorphisms (SNPs) using TaqMan assays. The genotype frequencies were evaluated in all cases of cerebral palsy, and in subgroups based on gestational age (<37 or ≥37 weeks), the type of cerebral palsy (diplegia, hemiplegia, or quadriplegia), and gender. Logistic regression models were used to assess associations between genotypic distributions and CP. The risk for CP in both gestational age groups was significantly associated with polymorphisms of 2 SNPs: inducible nitric oxide synthase (iNOS) and lymphotoxin a (also called LTA or tumor necrosis factor β (TNF-β). For iNOS, presence of the T allele was more common in all children with CP and among heterozygotes born at term. Homozygous variant status for LTA was associated with risk for CP and with spastic hemiplegic or quadriplegic CP. In addition to iNOS, heterozygosity for the endothelial protein C receptor SNP was more frequent among children with CP. Among infants born preterm, the variant A allele of interleukin 8 and heterozygosity for the β-2 adrenergic receptor were associated with CP. Interleukin 8 heterozygosity was associated with spastic diplegia. Some gene variants were found in girls with CP but not in boys. These findings, together with previous studies, suggest that certain genes are associated with increased susceptibility to CP.

Diagnostic et prise en charge des maladies neurométaboliques en Tunisie. Étude prospective sur trois ans

Introduction Neurometabolic diseases are a large group of genetic diseases. In our country, the diagnostic and therapeutic approach to theses diseases is rather difficult. The aim of our study was to determine the frequency of neurometabolic diseases in the hospital population, to describe the problems in diagnosing these conditions and difficulties encountered during patient care. Our goal was to propose guidelines for a practical diagnostic and therapeutic approach to neurometabolic disorders in our country. Methods We have conducted a prospective study over a 3-year period including all patients diagnosed with “metabolic disease” and followed at the Child and Adolescent Neurology Department of the National Institute of Neurology of Tunis. Results One hundred and thirty-six patients were included (2.4% of our patients). Mean age was 7.3 ± 5.1 years. Mean age at onset was 4.3 years. There was a high consanguinity rate. Respiratory chain defects were the most frequently suspected diseases (16.9%), followed by lysosomal diseases (8.8%). Chromatography, initially systematically prescribed, became targeted with a higher diagnostic efficacy. Metabolic diseases diagnosed as certain, represented 22% of the studied cases. This can be explained by the insufficiency of available laboratory tests of confirmation. The prescription of specific treatment was insufficient, even for confirmed pathologies (14.7%) because of the high cost of these therapies. Conclusion The diagnostic approach has to be rational, targeted, multidisciplinar and conducted within a care network. Diagnostic priority should focus on treatable neurometabolic diseases. The establishment of a systematized registry and neonatal screening for the main treatable neurometabolic diseases constitute the final objective of our work to prepare for biochemical and genetic studies.

&lt;p&gt;Causes of childhood deafness in Pukhtoonkhwa Province of Pakistan and the role of consanguinity&lt;/p&gt;

Background: Deafness is the hidden disability of childhood, and leads to poor educational and employment prospects. There is little published information on deafness in Pakistan. Profound hearing impairment is more prevalent in countries where consanguineous marriages are common, such as Pakistan. This study aimed to assess causes of childhood deafness and association with parental consanguinity, within deaf and hearing children in the Peshawar district of Pukhtoonkhwa Province, Pakistan.&#x0D; Methods: One hundred and forty deaf children were identified from two schools for deaf children within the Peshawar district. These children were assessed via audiology, otoscopic examination, case note review and parental history, in order to attempt to ascertain the cause of their deafness. Two hundred and twenty-one attendees at a local immunisation clinic (taken as representative of the local childhood population) were also screened for hearing impairment. Parents of both groups of children were assessed by interview and questionnaire in order to ascertain the mother and father’s family relationship (i.e., whether cousins or unrelated).&#x0D; Results: Of the 140 deaf school pupils, 92.1 per cent were profoundly hearing impaired and 7.9 per cent were severely hearing impaired. All these children had bilateral sensorineural hearing loss. A possible cause of deafness was identified in only six of these children. Parental consanguinity (i.e., first or second cousins) was established for 86.4 per cent of deaf school pupils and 59.7 per cent of immunisation clinic attendees. None of the control children were identified as having a hearing problem.&#x0D; Conclusion: The prevalence of parental consanguinity was significantly higher in deaf children compared with nonhearing impaired children. However, the study also confirmed a high rate of consanguinity within the general Peshawar community. In this setting, prevention of consanguineous unions is the only means of reducing levels of congenital hearing impairment. The current levels of hearing disability represent both a prominent public health problem and an important, potentially preventable childhood disability.&#x0D; Published courtesy of:J Laryngol Otol. 2008; 21:1-7

WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon

Most cases of juvenile-onset diabetes (JOD) are diagnosed as type 1 diabetes (T1D), for which genetic studies conducted in outbred Caucasian populations support the concept of multifactorial inheritance. However, this view may be partly challenged in particular population settings. In view of the suggestive evidence for a high prevalence of Wolfram syndrome (WFS) in Lebanon, the phenotypic variability associated with WFS1 mutations, and the high consanguinity rate in Lebanon, we aimed to evaluate the contribution of WFS1 mutations as monogenic determinants to JOD in Lebanon. We performed a family-based genetic study, with linkage analysis followed by systematic mutation screening of WFS1 exons in all JOD probands. The study population consisted of an unbiased recruitment of all juvenile-onset insulin-dependent diabetic patients from a specialized diabetes pediatric clinic in Beirut, Lebanon. Homozygous or compound heterozygous WFS1 mutations were found in 22 of the 399 JOD probands (5.5%), resulting in WFS (17 probands) or in non-syndromic non-autoimmune diabetes mellitus (DM, five probands). These accounted for 12.1% (21/174) of probands in consanguineous families, compared with 0.4% (1/225) in non-consanguineous families. Of the 38 patients identified with homozygous or compound heterozygous WFS1 mutations, 11 (29%) had non-syndromic DM, all of whom carried a particular WFS1 mutation, WFS1(LIB), encoding a protein with an extended C-terminal domain. This mutation resulted in a delayed onset or absence of extrapancreatic features. These results underscore the major impact of population-specific factors, such as population-specific mutations and founder effects, and family structure in the genetic determinism of JOD.

Consanguineous Iranian kindreds with severe Tourette syndrome

The search for vulnerability genes for Tourette syndrome has been ongoing for nearly three decades. The contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. Homozygosity mapping has been successfully used to detect recessive loci within populations with high rates of consanguinity. Using this technique, even quite small inbred families can be informative due to autozygosity in which the two alleles at an autosomal locus are identical by descent (i.e., copies of a single ancestral gene). To explore the utility of this approach, we identified 12 consanguineous Iranian families. Remarkably, these families were seen with an unusual natural history characterized by the early onset of vocal tics and coprolalia and frequent comorbidity with obsessive-compulsive disorder. Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder.

Consanguinity and major genetic disorders in Saudi children: a community-based cross-sectional study

BACKGROUND AND OBJECTIVESThere is a high rate of consanguinity in Saudi Arabia; however, information on its relationship with genetic disorders is limited. The objective of this cross-sectional study was to explore the role of consanguinity in genetic disorders.SUBJECTS AND METHODSThe study sample was determined by a multistage probability random sampling procedure. Consanguinity status was obtained during household visits. Primary care physicians performed a history and physical examination of all children and adolescents younger than 19 years, and all cases of genetic diseases were recorded. The chi-square test was used to compare proportions.RESULTSDuring the two-year study period (2004–2005), 11 554 of 11 874 (97%) mothers answered the question on consanguinity, and 6470 of 11 554 (56%) were consanguineous. There was no significant association between first-cousin consanguinity and Down syndrome (P=.55). Similarly, there was no significant association with either sickle cell disease (P=.97) or glucose-6-phosphate dehydrogenase deficiency (P=.67) for first-cousin consanguinity. A borderline statistical significance was found for major congenital malformations (P=.05). However, the most significant association with first-cousin consanguinity was congenital heart disease (CHD) (P=.01). Finally, no significant association was found for type 1 diabetes mellitus (P=.92). For all types of consanguinity, similar trends of association were found, with a definite statistically significant association only with CHD (P=.003).CONCLUSIONThe data suggest a significant role of parental consanguinity in CHD. However, a relationship between consanguinity and other genetic diseases could not be established. The effect of consanguinity on genetic diseases is not uniform and this should be taken into consideration in genetic counseling.

Causes of childhood deafness in Pukhtoonkhwa Province of Pakistan and the role of consanguinity

Deafness is the hidden disability of childhood, and leads to poor educational and employment prospects. There is little published information on deafness in Pakistan. Profound hearing impairment is more prevalent in countries where consanguineous marriages are common, such as Pakistan. This study aimed to assess causes of childhood deafness and association with parental consanguinity, within deaf and hearing children in the Peshawar district of Pukhtoonkhwa Province, Pakistan. One hundred and forty deaf children were identified from two schools for deaf children within the Peshawar district. These children were assessed via audiology, otoscopic examination, case note review and parental history, in order to attempt to ascertain the cause of their deafness. Two hundred and twenty-one attendees at a local immunisation clinic (taken as representative of the local childhood population) were also screened for hearing impairment. Parents of both groups of children were assessed by interview and questionnaire in order to ascertain the mother and father's family relationship (i.e. whether cousins or unrelated). Of the 140 deaf school pupils, 92.1 per cent were profoundly hearing impaired and 7.9 per cent were severely hearing impaired. All these children had bilateral sensorineural hearing loss. A possible cause of deafness was identified in only six of these children. Parental consanguinity (i.e. first or second cousins) was established for 86.4 per cent of deaf school pupils and 59.7 per cent of immunisation clinic attendees. None of the control children were identified as having a hearing problem. The prevalence of parental consanguinity was significantly higher in deaf children compared with non-hearing impaired children. However, the study also confirmed a high rate of consanguinity within the general Peshawar community. In this setting, prevention of consanguineous unions is the only means of reducing levels of congenital hearing impairment. The current levels of hearing disability represent both a prominent public health problem and an important, potentially preventable childhood disability.

The Signatures of Autozygosity among Patients with Colorectal Cancer

Previous studies have shown that among populations with a high rate of consanguinity, there is a significant increase in the prevalence of cancer. Single nucleotide polymorphism (SNP) array data (Affymetrix, 50K XbaI) analysis revealed long regions of homozygosity in genomic DNAs taken from tumor and matched normal tissues of colorectal cancer (CRC) patients. The presence of these regions in the genome may indicate levels of consanguinity in the individual's family lineage. We refer to these autozygous regions as identity-by-descent (IBD) segments. In this study, we compared IBD segments in 74 mostly Caucasian CRC patients (mean age of 66 years) to two control data sets: (a) 146 Caucasian individuals (mean age of 80 years) who participated in an age-related macular degeneration (AMD) study and (b) 118 cancer-free Caucasian individuals from the Framingham Heart Study (mean age of 67 years). Our results show that the percentage of CRC patients with IBD segments (>or=4 Mb length and 50 SNPs probed) in the genome is at least twice as high as the AMD or Framingham control groups. Also, the average length of these IBD regions in the CRC patients is more than twice the length of the two control data sets. Compared with control groups, IBD segments are found to be more common among individuals of Jewish background. We believe that these IBD segments within CRC patients are likely to harbor important CRC-related genes with low-penetrance SNPs and/or mutations, and, indeed, two recently identified CRC predisposition SNPs in the 8q24 region were confirmed to be homozygous in one particular patient carrying an IBD segment covering the region.

Consanguinity and family clustering of male factor infertility in Lebanon

To investigate the influence of consanguineous marriage on male factor infertility in Lebanon, where rates of consanguineous marriage remain high (29.6% among Muslims, 16.5% among Christians). Clinic-based, case-control study, using reproductive history, risk factor interview, and laboratory-based semen analysis. Two IVF clinics in Beirut, Lebanon, during an 8-month period (January-August 2003). One hundred twenty infertile male patients and 100 fertile male controls, distinguished by semen analysis and reproductive history. None. Standard clinical semen analysis. The rates of consanguineous marriage were relatively high among the study sample. Patients (46%) were more likely than controls (37%) to report first-degree (parental) and second-degree (grandparental) consanguinity. The study demonstrated a clear pattern of family clustering of male factor infertility, with patients significantly more likely than controls to report infertility among close male relatives (odds ratio = 2.58). Men with azoospermia and severe oligospermia showed high rates of both consanguinity (50%) and family clustering (41%). Consanguineous marriage is a socially supported institution throughout the Muslim world, yet its relationship to infertility is poorly understood. This study demonstrated a significant association between consanguinity and family clustering of male factor infertility cases, suggesting a strong genetic component.

Lafora disease in the Indian population:EPM2A andNHLRC1 gene mutations and their impact on subcellular localization of laforin and malin

Lafora disease (LD) is a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. LD is more common among geographic isolates and in populations with a higher rate of consanguinity. Mutations in two genes, EPM2A encoding laforin phosphatase, and NHLRC1 encoding malin ubiquitin ligase, have been shown to cause the LD. We describe here a systematic analysis of the EPM2A and the NHLRC1 gene sequences in 20 LD families from the Indian population. We identified 12 distinct mutations in 15 LD families. The identified novel mutations include 4 missense mutations (K140N, L310W, N148Y, and E210 K) and a deletion of exon 3 for EPM2A, and 4 missense mutations (S22R, L279P, L279P, and L126P) and a single base-pair insertional mutation (612insT) for NHLRC1. The EPM2A gene is known to encode two laforin isoforms having distinct carboxyl termini; a major isoform localized in the cytoplasm, and a minor isoform that targeted the nucleus. We show here that the effect of the EPM2A gene mutation L310W was limited to the cytoplasmic isoform of laforin, and altered its subcellular localization. We have also analyzed the impact of NHLRC1 mutations on the subcellular localization of malin. Of the 6 distinct mutants tested, three targeted the nucleus, one formed perinuclear aggregates, and two did not show any significant difference in the subcellular localization as compared to the wild-type malin. Our results suggest that the altered subcellular localization of mutant proteins of the EPM2A and NHLRC1 genes could be one of the molecular bases of the LD phenotype.

Consanguinity and deafness in Omani children

This study was based on a national retrospective analysis of 1400 questionnaires on the causes of deafness in Omani children, collected from 1986 to 2000. It was found that 70% of the deaf children were from parents of consanguineous marriages, and 30% from non-consanguineous unions. In those with consanguineous families 70.16% were first cousin marriages, 17.54% were second cousins, and 10.86% were from the same tribe. The proportion arising from first cousin marriages was higher than the background rate of first cousin marriages in Oman. In the total cohort, 45% had other family members with hearing loss. There was a greater chance of other relatives being affected in the consanguineous group as opposed to the non-consanguineous group (29.7% versus 15.3%). In most cases the affected relative was a deaf sibling (67.8%). We have demonstrated a higher rate of consanguinity amongst parents of deaf children in Oman and suggest this is associated with a higher frequency of autosomal recessive deafness in this paediatric population.

Newborn Haemoglobinopathy Carrier Screening: Towards Comprehensive and Improved Patient Care of Sickle Cell Disease in Oman, a Cost Effective Analysis.

Objective: The aim of the study was to establish neonatal cord blood screening in the Sultanate of Oman, in an effort to determine the prevalence of haemoglobinopathies by a cost-effective method.Background: Oman is a country with a two million population comprising of a wide range of ethnic groups, high rates of consanguinity and increased incidences of inter-cousin marriages all leading to an increased prevalence of haemoglobinopathies. High performance liquid chromatography [HPLC] is a powerful tool to screen newborns for haemoglobinopathies. Neonatal screening includes cord blood samples collection, screening and follow up of all newborns with abnormal results.Methods: A total of 7837 consecutive cord blood samples were screened for the presence of possible haemoglobinopathies by HPLC using Biorad Variant II program between April 2005 & March 2007. Complete blood counts [CBC] were also obtained on Cell Dyn 4000 automated blood cell counter. All samples were then processed to isolate and store mononuclear leukocytes for subsequent molecular diagnostics.Results: The findings indicated a 47.07% incidence of α-thalassaemia, based on low mean cell volume [MCV] & mean cell haemoglobin [MCH] on the CBC and significant amounts of Hb Barts on HPLC. Furthermore, the overall incidence of other haemoglobinopathies was 9.87%, with 5.47% incidence of sickle haemoglobin. On HPLC, D-window, E-window and C-window were present in 0.93%, 0.77% and 0.06% of the samples respectively. [Display omitted] Since HPLC cannot diagnose beta thalassemia major at birth, in samples with HbA below 10%, the beta globin gene was directly sequenced including the promoter, all exons and introns in these samples. Amongst 206(2.62%) samples sequenced, beta thalassaemia trait was confirmed in 201 cases and 5 cases were homozygous for beta thalassaemia. Additionally, direct sequencing of all abnormal samples with HbS,[n=429] HbD,[n=73], HbE[n=42] and HbC[n=5] was also performed on ABI 3100 Genetic Analyzer to assign the genotype status to these subjects and to validate the HPLC results. Amongst the 429 samples with HbS sequenced, 24 samples were homozygous (0.3%) and were referred for comprehensive clinical care programme.Conclusions: The significantly high incidence of haemoglobinopathies in newborns in the Sultanate of Oman emphasizes the value of neonatal cord blood screening to be implemented as the first step in the national strategy towards total management of haemoglobinopathies including early diagnosis, comprehensive clinical care and counseling of the affected families. The results of this large study indicate that using HPLC [<2 USD/sample] and prescreening of parents to select only abnormal samples for neonatal cord blood screening [<10% samples] can be recommended as a highly cost-effective method targeted to screen only the abnormal samples.

Characteristics of Fibromyalgia in Muslim Bedouin Women in a Primary Care Clinic

Fibromyalgia (FM) has been described and studied in various sociocultural settings in both developed and developing countries. To study the clinical manifestations of FM and to describe its effect on quality of life in the unique setting of Muslim Bedouin women in the southern Israel Negev desert area. One hundred two Bedouin women were recruited from a primary health care clinic in the Negev area. All patients fulfilled American College of Rheumatology criteria for the diagnosis of FM. Tenderness was assessed by manual dolorimetry and the fibromyalgia impact questionnaire was utilized to estimate the severity of FM symptoms. Anxiety and depression were assessed by the Arthritis Impact Measurement Scales subscales and quality of life was evaluated by the SF-36 questionnaire. The study population was characterized by a low educational level, a high rate of consanguinity, a high number of children per mother, and a high rate of polygamy. There was a high frequency of classic FM symptoms such as pain and fatigue, as well as anxiety and depression. The overall impact of FM on quality of life was exceedingly high (8.9 on a scale of 0 to 10). FM is relatively common in the unique setting of Muslim Bedouin women and has a very significant impact on their quality of life as well as on their dependents. Physicians involved in the primary care of this population should be attentive to the manifestations of FM and related disorders.

Caractéristiques cliniques des patients bipolaires type I en fonction de leurs antécédents familiaux thymiques

Caractéristiques cliniques des patients bipolaires type I en fonction de leurs antécédents familiaux thymiques

Index of Suspicion in the Nursery

Five days after birth at a private hospital, an infant is brought to another hospital because he is inactive and limp. The delivery was by outlet forceps after a supervised, normal pregnancy to consanguineous (uncle-niece) parents. His birthweight was 3.25 kg. According to his parents, he did not cry until 1 hour after birth, was limp, fed poorly, and a few hours later, had cyanosis of lips and nails and generalized tonic and clonic convulsions that were unresponsive to anticonvulsants and intravenous glucose. The parents were told that he had hypoxic brain injury and possibly an intracranial hemorrhage. The convulsions became less frequent once expressed human milk was provided through a nasogastric tube. The exact details of management at the private hospital are not available. The infant is the first child of the woman, who is well nourished and does not have diabetes. His weight on admission at 5 days of age is 3.66 kg, length is 49 cm, and head circumference is 33 cm. He is inactive and limp. His temperature is 97.8°F (36.6°C) and heart rate is 170 beats/min. His cry is feeble and response to pain is minimal. His anterior fontanelle is normal, hydration is adequate, Moro reflex is incomplete, and sucking and rooting reflexes are poor. He does not have syndromic features or acidosis. No additional findings are revealed in the remainder of the general and systemic evaluations. The results of a complete blood count; measurement of electrolytes, calcium, and bilirubin; review of the cerebrospinal fluid and urinalysis; electrocardiography and radiography of the chest and skull; and abdominal ultrasonography are normal. Cultures of blood, cerebrospinal fluid, and urine are sterile. Oxygen saturation is 98%. Blood glucose on admission is 41 mg/dL (2.28 mmol/L) and is monitored every 1 to 4 hours. Urine ketones are negative. The …

Epidemiology, clinical and complications profile of diabetes in Saudi Arabia: a review.

Diabetes mellitus is emerging as a major public health probelm in Saudi Arabia in parallel with the worldwide diabetes pandemic, which is having a particular impact upon the Middle East and the third world. This pandemic has accompanied the adoption of a modern lifestyle and the abandonment of a traditional lifestyle, with a resultant increase in rates of obesity and other chronic non-communicable diseases. The indigenous Saudi population seems to have a special genetic predisposition to develop type 2 diabetes, which is further amplified by a rise in obesity rates, a high rate of consanguinity and the presence of other variables of the insulin resistance syndrome. We highlight the epidemiology, clinical and complications profiles of diabetes in Saudi people. Diabetes is well studied in Saudi Arabia; however, there seems to be little research in the area of education and health care delivery. This is of paramount importance to offset the perceived impact on health care delivery services, to lessen chronic diabetes complications, and to reduce the expected morbidity and mortality from diabetes.

Implementation of extended neonatal screening and a metabolic unit in the State of Qatar: Developing and optimizing strategies in cooperation with the Neonatal Screening Center in Heidelberg

Qatar is a country in the Gulf area and member of the Gulf Cooperation Council states. The country is populated by original Qatari tribes that amount to about 200,000 people and about 600,000 expatriates mainly from Arabic and Asian countries. Inbreeding over centuries and high rates of consanguinity in the Qatari population and in some groups of expatriates, in addition to large family sizes and rapid population growth, have contributed to a high frequency of autosomal recessive disorders. In December 2003 Hamad Medical Corporation in Doha and the University Children's Hospital of Heidelberg, Germany, started an extended state-wide neonatal screening programme for metabolic and endocrine disorders, with the laboratory situated in Heidelberg, Germany. All aspects of the screening process had to be adapted to the unique situation of the laboratory being 6000 km from the birthplace of the neonates. Within 32 months, samples of 25,214 neonates were screened. In 28 cases an endocrine or metabolic diagnosis was identified (incidence 1:901, in Germany 1:1728). In particular, a variety of monogenic metabolic diseases were prevalent, with 19 patients detected giving an incidence of metabolic diseases of 1:1327 (Germany 1:2517). Each euro spent on the screening programme saved more than 25 euros in health and social costs. The programme revealed a high incidence of treatable inborn metabolic diseases in the population of Qatar. A reliable screening for classical homocystinuria showing a unique incidence of >1:3000 and for sickle cell disease has now been added.

Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations

Reports on genetically informative steroid-responsive (sensitive) idiopathic nephrotic syndrome (SSNS) families are lacking. We studied an extended SSNS Bedouin (B) family with a high rate of consanguinity. The clinical presentation and steroid response of its 11 affected individuals were similar to those of sporadic SSNS (spontaneous remission towards puberty and minimal change disease by kidney biopsy). Genome-wide linkage analysis, using a 382 microsatellite-markers mapping set and additional markers adjacent to 80 candidate genes of the index family, did not support linkage to any chromosomal locus. Retrospective analysis of all additional children with SSNS treated by our institution in the past 20 years (n=96, 50% of them of Jewish origin) revealed another five non-related B families with 2-3 first-degree cousins affected with SSNS in each. The overall familial SSNS rate among the B population (excluding the index family) was 28%, compared with 4% among Jews (Js) (OR 1.8-64, P<0.005). There were more Bs with simple SSNS than there were Js (71% and 40%, respectively; OR 3.58, 95% CI 1.41-9.23, P<0.01). In summary, SSNS in this index family was not linked to any of the presently known chromosomal loci nor predicted to be caused by mutation in any one of a list of genes associated with nephrotic syndrome (NS). The presence of other B families affected by SSNS supports the role for susceptibility genes enrichment, exposing highly consanguineous populations to an increased incidence of SSNS.