High Rate Of Consanguinity Research Articles

Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population

Neuromuscular diseases (NMDs) include a broad range of disorders affecting muscles, nerves and neuromuscular junctions. Their overlapping phenotypes and heterogeneous genetic nature have created challenges in diagnosis which calls for the implementation of massive parallel sequencing as a candidate strategy to increase the diagnostic yield. In this study, total of 45 patients, mostly offspring of consanguineous marriages were examined using whole exome sequencing. Data analysis was performed to identify the most probable pathogenic rare variants in known NMD genes which led to identification of causal variants for 33 out of 45 patients (73.3%) in the following known genes: CAPN3, Col6A1, Col6A3, DMD, DYSF, FHL1, GJB1, ISPD, LAMA2, LMNA, PLEC1, RYR1, SGCA, SGCB, SYNE1, TNNT1 and 22 novel pathogenic variants were detected. Today, the advantage of whole exome sequencing in clinical diagnostic strategies of heterogeneous disorders is clear. In this cohort, a diagnostic yield of 73.3% was achieved which is quite high compared to the overall reported diagnostic yield of 25% to 50%. This could be explained by the consanguineous background of these patients and is another strong advantage of offering clinical exome sequencing in diagnostic laboratories, especially in populations with high rate of consanguinity.

Challenges identified in the management of patients with inherited metabolic disorders – A five year experience from Pakistan

BackgroundPakistan is the sixth most populous country in the World. High rates of consanguinity and inter caste marriages have resulted in a substantial burden of inherited metabolic disorders (IMDs). Despite this load, there is a dearth of both medical genetic and clinical metabolic services in Pakistan. There are inadequate numbers of appropriately trained clinicians, ill-equipped laboratories, lack of scientists and technologists equipped with skills to deal with the challenging laboratory investigations involved in IMD and a health care infra-structure unable to support a service. AimWe present the first five year experience of the first established metabolic unit at a tertiary care hospital in Pakistan and present the case for screening of parents, parents’ siblings and antenatal diagnostic testing in subsequent pregnancies in order that families can make informed choices in preventing recurrence. Subjects and methodsThis retrospective observational study comprising of patients’ chart review was conducted in the Department of Paediatrics, AKUH Karachi in Pakistan for patients who presented to the Clinical Genetics unit from January 2008 to December 2012 seeking diagnosis and treatment for the underlying IMD. ResultsWe evaluated 426 children, of which, 333 (78%) had consanguineous parents. Most patients, 151 (35%). evaluated for IMD were between 1year and 5years of age. Developmental delay, seizures, hypotonia, microcephaly, neuroregression, dystonia, ataxia and encephalopathy were the most common reasons for referrals. Only 155 (36%) patients underwent metabolic biochemical testing. Among the investigated group of patients, diagnoses were established for 85 (55%) patients equivalent to only 19.8% of the total. ConclusionNeonatal screening for IMDs and their treatment in the current situation is an unaffordable practical option in Pakistan. Screening parents, siblings and subsequent pregnancies, however, is likely to provide a cost effective and acceptable alternative in reducing the burden and enabling early, effective detection of affected progeny before the stage when neurometabolic changes become irreversible in developing countries like Pakistan with very limited resources.

Elevated birth prevalence of conotruncal heart defects in a population with high consanguinity rate.

The aetiology of conotruncal heart defects is poorly understood and the birth prevalence varies geographically. The known risk factors for developing conotruncal heart defects are as follows: CHD in siblings, genetic chromosomal abnormalities, paternal age >30 years, high parity, low birth weight, prematurity, and maternal diabetes. The aim of this study was to characterise conotruncal heart defects, birth prevalence, mortality, and morbidity in the population of southern Israel, of whom 75% are Jewish and the rest are mostly Bedouin Arabs. The data were obtained from Soroka University Medical Center database of births and newborns. Conotruncal heart defects cases were identified by ICD9 codes. During 1991-2011, there were 247,290 singleton live births and 393 conotruncal heart defects in Soroka University Medical Center. The birth prevalence per 10,000 live births of tetralogy of Fallot, transposition of the great arteries, and truncus arteriosus was 9.5, 5, and 1.8, respectively. In the multivariate analysis, Bedouin descent (adjusted odds ratio 2.40, p35 years (1.66, p=0.004), and siblings with congenital heart defects (1.98, p=0.005) were associated with tetralogy of Fallot, and Bedouin descent (1.61, p=0.05), siblings with congenital heart defects (2.19, p=0.004), and diabetes mellitus (7.15, p<0.001) were associated with transposition of the great arteries. In a univariate analysis, Bedouin descent (p=0.004) and congenital heart defects in siblings (p<0.001) were associated with truncus arteriosus. We observed higher birth prevalence of conotruncal heart defects compared with the birth prevalence reported worldwide, specifically among the Bedouins, a population characterised with high consanguinity rate. Therefore, genetic counselling and early fetal echocardiograms should be encouraged, especially in high consanguinity rate populations. Naturally, further educational efforts are needed in order to decrease consanguinity and its related consequences.

Current Status of Childhood Hyperinsulinemic Hypoglycemia in Turkey.

Congenital hyperinsulinism (CHI) is a rare disease characterized by dysregulated insulin secretion from pancreatic β-cells. Recurrent hypoglycemia can lead to neurological insult and permanent brain injury. Recently, there are important advances in understanding the genetic mechanisms, histological characteristics, imaging, and surgical techniques of congenital hyperinsulinemic hypoglycemia that could reflect to improvement in the clinical care of infants with this disorder. In Turkey, there is a high rate of consanguinity, thus, the incidence of CHI is expected to be high. Until now, there are no nationwide data regarding the disorder, and some individual case reports or case series had been published. Determining the characteristics of Turkish patients with CHI can help develop a different perspective on this rare disease. In this review, we evaluated the clinical and molecular characteristics of Turkish patients with CHI based on reports published in the literature. The most frequently seen mutations were ABCC8 gene mutations (n=37), followed by HADH (n=11) and KCNJ11 gene (n=7) mutations. A total of 141 Turkish patients with CHI were reported until now. Among them, 115 patients had been genetically analyzed, and 56 of them had one of the mutation leading to hyperinsulinism.

Successful Linkage Analysis in Classical Phenylketonuria Families Followed by Direct Sequencing and Mutation Detection.

Phenylketonuria (PKU) is the most common disorder of inborn errors of metabolism. Prevalence of PKU is about 1:10000 live births; however, due to high rate of consanguinity in the Middle East and North of Africa the prevalence of PKU is more than in other areas. It is estimated between 1:2600 in Turkey and 1:3672 in Iran. The best way to identify carriers in PKU families is studying causative mutations, but this approach could be costly and time consuming. As a result, linkage analysis can be considered as a reliable way to detect carriers. Ten non-related classical PKU families from Iran-Fars province were enrolled. Linkage analysis was performed through application of highly linked genetic markers to the PAH gene (VNTR, PAHSTR, and XmnI marker) with new designed primers for polymerase chain reaction (PCR). Reliability of approach was assessed by Sanger sequencing, mutation detection, and capillary electrophoresis (CE). Through application of linkage analysis, nine out of ten families were genotyped successfully. Heterozygosity of chromosome 12 was not detected in any of the enrolled PKU patients. Specificity of new designed primers for linkage analysis was confirmed by Sanger dideoxy sequencing. Results obtained from linkage analysis were confirmed by direct sequencing and detecting causative mutations in half of the genotyped families. All the results were the same as the linkage analysis results. Labeled primers were capable and linkage analysis by CE was successful. Linkage analysis is a powerful and reliable approach for detecting carriers in PKU families which have not been previously screened for causative mutations. We suggest studying the feasibility of the approach in preliminary diagnosis of PKU and confirming autozygosity of chromosome 12, prenatal diagnosis, and preimplantation genetic testing. Also, we recommend using labeled primers for constructing faithful local PKU associated haplotype databases to provide fast, cheap, and reliable detection of causative mutations in new cases of hyperphenylalaninemia.

Biochemical, radiological, and genetic characterization of congenital hypothyroidism in Abu Dhabi, United Arab Emirates.

Congenital hypothyroidism (CH) is caused by thyroid gland (TG) dysgenesis or inadequate thyroid hormone biosynthesis in a structurally normal gland. Different etiologies are known to be associated with various clinical, biochemical and imaging markers and a subset of cases have an underlying genetic basis. Despite the presence of neonatal screening programs in the UAE, there is a lack of data on the disease etiology in the area. We aim to study the etiology of CH in our center and examine its relationship with the clinical, biochemical, genetic and radiological features. Patients with CH who were followed in our center between 2011 and 2014 are enrolled in the study. Data collected included gender, gestational age, history of CH in a first-degree relative, initial thyroid stimulating hormone (TSH) and thyroxine (T4) levels, imaging findings, associated disease/malformation and treatment details. Selected patients with associated systemic disease or familial CH underwent genetic testing. Sixty-five patients were enrolled. Ten patients underwent genetic study: seven patients with associated congenital disease/malformation, one with a sibling and two with cousins with CH. Forty-nine subjects had technetium99 and/or ultrasound scans. Dyshormonogenesis was diagnosed in two-thirds of the patients. Three patients of 10 tested had likely causative genetic mutations; two homozygous thyroid peroxidase (TPO) and one heterozygous thyroid stimulating hormone receptor (TSHR) missense mutations. Dyshormonogenesis is the commonest etiology in CH in the studied group. It is expected that genetic mutations are more prevalent in our region due to the nature of the CH etiology and the rate of high consanguinity rate.

Consangunity and psychosis in Algeria. A family study

Several studies have affirmed the existence of a strong and complex genetic component in the determination of psychotic disorders. However, the genetic architecture of these disorders remains poorly understood. GWAS studies conducted over the past decade have identified some associations to low effect, and the major part of this heritability remains unexplained, thus calling into question the hypothesis of “common disease – common variant” for model involving a large number of rare variants. Family studies of extended pedigrees selected from geographical isolate can be a powerful approach in identifying rare genetic variants of complex diseases such as psychotic disorders. Here, we studied four multigenerational families in which co-exist psychotic and mood disorders and a high rate of consanguinity, identified in the northwest of Algeria. This case-control study aimed to characterize new rare genetic variants responsible for psychosis. These families have received complete clinical and genealogical investigations, genome wide analysis that were performed in the laboratory of medical genetics in the university hospital of Geneva. A genome wide research CNVs using Agilent Human Genome CGH Microarray Kit 44 K, covering 45 subjects including 20 patients and in a control population of 55 individuals. Three CNVs that had never been reported to date have been identified in one of four families and validated by two techniques. It is the dup 4q26, and 16q23.1 del del21q21. These CNVs are transmitted by either parent line, suggesting a cumulative effect on the risk of psychotic disorders. Further analyzes using pan-genomic linkage analysis using GWAS chip (Illumina Human 660 W-Quad v1.0 Breadchip) and complete WES (by GAIIx Illumina/HiSeq 2000) were performed in some related individuals to search other mutations may explain the appearance of the phenotype in this population.

Hematopoietic stem cell transplantation from non-sibling matched family donors for patients with thalassemia major in Jordan.

There are limited data on the outcome of patients with thalassemia receiving HSCT from non-sibling matched family donors. Of the 341 patients with thalassemia major that underwent donor search at our center from January 2003 to December 2011, 236 (69.2%) had fully matched family donor of which 28 patients (8.2%) had non-sibling matched family donors identified. We report on seven patients with a median age of eight yr (4-21) who underwent myeloablative (n = 4) or RIC (n = 3) HSCT. The median age of the donors was 33 yr (4-47), three were parents, two first cousins, one paternal uncle, and one paternal aunt. All patients achieved primary neutrophil and platelet engraftment at a median of 18 (13-20) and 16 days (11-20), respectively. One patient developed grade II acute GVHD, and two patients developed limited chronic GVHD. One patient experienced secondary GF requiring a second transplant. At a median follow-up of 69 months (7-110), all patients are alive and thalassemia free. Our data emphasize the need for extended family HLA typing for patients with thalassemia major in regions where there is high rate of consanguinity. Transplant from non-sibling matched family donor can result in excellent outcome.

Screening for inherited metabolic disorders in patients with Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autosomal recessive auto-inflammatory disease, presenting with recurrent episodes of fever and polyserositis. Diagnosis of FMF is may be challenging especially in pediatric population. Mitochondrial fatty acid oxidation disorders and porphyrias can present with periodic abdominal and muscle pain. Incidence of both FMF and inherited metabolic disorders (IMD) are increased in Turkish patients partially due to high consanguinity rates.

Macrozoospermia: screening for the homozygous c.144delC mutation in AURKC gene in infertile men and estimation of its heterozygosity frequency in the Tunisian population.

Macrozoospermia is a rare condition of male infertility characterized by the presence of close to 100% large-headed multiflagellar spermatozoa. The homozygous mutation (c.144delC) in aurora kinase C gene (AURKC) has been identified as the most frequent mutation causing macrozoospermia in North African patients. The aim of this study was to evaluate the prevalence of this condition in Tunisia and estimate the frequency of c.144delC mutation among infertile and control populations. Sequencing c.144delC mutation was carried out in 33 macrozoospermic patients among 6652 infertile men. Minisequencing of exon3 was performed in 250 unrelated control individuals to estimate the frequency of c.144delC heterozygosity. More than 80% of macrozoospermic patients were c.144delC homozygous. The prevalence of homozygous c.144delC was 0.4% among infertile men (27/6652). The frequency of heterozygosity was 0.4% among controls (1/250). Surprisingly, it is five times less common than established in the general population of North Africa (2%) or in the Moroccan population (1.7%). We show that this mutation is relatively less frequent in the Tunisian population than in other Maghrebian populations. The occurrence of homozygous mutation among infertile men can be attributed to the high rate of consanguinity and its impact on the expression of this autosomal recessive male infertility disorder rather than a high frequency of heterozygous carriers among the general population. This highlights the importance of the molecular analysis of AURKC mutations for infertile men with high percentage of large-headed multiflagellar spermatozoa in order to limit unnecessary in vitro fertilization attempts for them.

A pilot study of spinal muscular atrophy carrier screening in Saudi Arabia

Spinal muscular atrophy (SMA), an autosomal recessive inherited disease, is a leading genetic killer under the age of two years. This disease is caused by mutation in the telomeric copy of the survival motor neuron gene ( SMN1 ). Most carriers of SMA have one chromosome 5 with a normal SMN1 gene and one with a deleted SMN1 gene. Although no large-scale population-based studies has been done in Saudi Arabia, previous estimations have indicated that incidence of SMA is much higher in Saudi population compared with other ethnic groups, partly because of high prevalence of consanguineous marriages. In this pilot study, we used a highly sensitive quantitative-polymerase chain reaction method to detect SMA carriers. Among 187 normal individuals not related to an SMA patient the carrier frequency was 5%, i.e. one carrier in each 20 persons compared to one in 50–80 in other parts of the world. Based on the results of this pilot study a new project is designed to further analyze the carrier status of SMA in Saudi population. This will shed more light on the magnitude of the problem of SMA in the countries with high rate of consanguinity.

Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene

Nephropathic cystinosis (NC) is an autosomal recessive disorder characterized by defective transport of cystine across the lysosomal membrane and resulting in renal, ophthalmic, and other organ abnormalities. Mutations in the CTNS gene cause a deficiency of the transport protein, cystinosin. This study was performed to investigate mutations of the CTNS gene in three Tunisian families with NC.Polymerase chain reaction (PCR), ARMS multiplex PCR and direct sequencing were performed for molecular characterization of the CTNS gene in 3 unrelated Tunisian patients and their parents. Based on family history, prenatal diagnosis (PND) was performed in fetal DNA isolated from chorionic villi obtained at 10–12 weeks of gestation.None of the patients showed the most common 57-kb deletion in heterozygous or homozygous status. One patient was homozygous for the previously reported mutation c.1515G>A (p.G308R). One patient presented the novel gross deletion of 20,327bp. One was homozygote for the previously reported mutation c.771_793del (p.Gly258Serfs*30). In addition, eight polymorphisms were identified in the 3 patients and their parents. The prenatal diagnosis in one family showed that the fetus DNA was heterozygous for the c.771_793del (p.Gly258Serfs*30) mutation.This study expands the mutational and population spectrum of NC, representing the first molecular diagnosis of NC in Tunisian population. The mutation screening of the CTNS gene was used for prenatal diagnosis to prevent and/or limit this inheritable disease in our country where the families are particularly large and have a high rate of consanguinity.

Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon.

Inherited metabolic disorders in Turkish patients with autism spectrum disorders.

Autism spectrum disorders (ASDs) are a major health problem because of their high prevalence in the general population. The pathophysiology of ASD remains unclear, although genetic defects may be detected in 10-20% of affected patients. Among these cases, the prevalence of inherited metabolic disorders (IMD) has not been extensively evaluated. IMDs responsible for ASDs are usually identified via clinical manifestations such as microcephaly, dysmorphic features, convulsions, and hepatosplenomegaly. Infrequently, patients with no additional clinical symptoms suggestive of an IMD may be diagnosed as having an idiopathic ASD. High consanguinity rates have resulted in an increased prevalence of IMDs in the Turkish population. The aim of this study was to explore the benefits of systematic screening for IMD among Turkish patients with ASDs. In our study, data were retrospectively collected for 778 children with ASDs. In all cases, the metabolic investigations included an arterial blood gas analysis, serum ammonia and lactate levels, a quantitative plasma amino acid analysis, a whole blood acylcarnitine profile via tandem mass spectrometry and a urine organic acid profile. Urinary glycosaminoglycan levels and homocysteine levels were screened in selected cases; 300 of the 778 patients with ASDs whose physical and metabolic investigations were complete and met this study's criteria were enrolled. Among the 300 children with autism, IMD were diagnosed in nine patients as follows: two patients were diagnosed with phenylketonuria, and one patient was diagnosed with partial biotinidase deficiency; one patient was diagnosed with mucopolysaccharidosis type III, and one patient was diagnosed with classical homocystinuria; one patient was diagnosed with glutaric acidemia type 1, and one patient was diagnosed with short chain acyl-CoA dehydrogenase deficiency; one patient was diagnosed with argininemia, and one patient was diagnosed with L-2-hydroxyglutaric aciduria.

Dental Morphological Markers as a Proxy for Ethnicity in Robinson Crusoe Islanders

*,**,***,**** ***** *** ****** ; ****** *** ** SUMMARY: Chilean Robinson Crusoe Island is a semi-isolated location with unusually high rates of both consanguinity and language disorder. The current population of 633 inhabitants is descended almost exclusively from the colonization at the end o f the 19th century, as there were few preceding immigrations to the island. This study investigates the genetic composition and degree of miscegenation within the island population, using dental morphological markers. The universe of island children was studied (n= 128, 3 to 15 years of age) using clinical exams, dental cast, and identification of each individual within a previously-constructed extensive genealo gy for the island. The frequencies for Carabelli's cusp (61.7%), shovel-shaped incisor (9.4%), and sixth cusp (2.3%), along with the absen ce of seventh cusp, are consistent with a primarily Caucasian population. The estimated degree of miscegenation suggests an Amerindia n component of 4.3%, which is consistent with the extensive known genealogies of the founders. Characterizing the genetic profile of Robinson Crusoe Island, a location with a remarkably high prevalence of language disorder, facilitates the comparison of the ge netic variants underlying this pathology with those identified in European populations.

Molecular analysis of patients with severe congenital factor X deficiency: First report from north and northwest of Iran.

Background Congenital FX deficiency is an extremely rare autosomal recessive disorder, mostly present in regions with a high rate of consanguinity, with an incidence of approximately 1:2,000,000 in the general population. The aim of this study was to evaluate the clinical manifestations and to provide a molecular analysis of 14 patients with homozygous factor X deficiency. Methods We evaluated the results of clinical and molecular characterization of 14 new cases (10 males, 4 females aged from 4 to 17 years) of FXD (FX activity <1%) in North and Northwest of Iran. FXD was diagnosed by clinical findings and routine laboratory tests. The PCR products of all the eight exons and their intron-exon boundaries were sequenced using DNA sequencer. Results Mean age of patients and mean age at diagnosis were 9 and 2.5 years, respectively. The molecular analysis revealed five different mutations, all of them were previously described. Molecular analysis showed five different homozygous and double heterozygous mutations including Arg-1Thr, Cys81Tyr, Gly78Asp, IVS1+3, and IVS2-3. Discussion The study of a large population of factor X patients from three institutions indicated that FXD was one of the most serious among rare bleeding disorders and that factor X gene mutation may be related to bleeding tendency in patients.

Rhodopsin mutations are scarcely implicated in autosomal recessive retinitis pigmentosa: A preliminary study of Egyptian retinitis pigmentosa patients

BackgroundRetinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations that is estimated to affect more than 1.5 million people worldwide. RP is characterized by retinal pigment deposits visible on fundus examination, abnormal electroretinogram and progressive retinal dysfunction. AimThe present work aimed to identify the possible mutations in the rhodopsin gene (RHO) among Egyptian RP patients as well as identifying the different inheritance patterns of those patients. Subjects and methodsThirty diagnosed retinitis pigmentosa patients were enrolled in the study. Inheritance forms of RP were identified by recording full family history, the coding regions of the rhodopsin gene were sequenced using blood-derived genomic DNA samples donated by patients and fifteen healthy controls. ResultsA high percentage of autosomal recessive cases was reported. Also a high parental consanguinity rates were evident. Sequencing of rhodopsin gene revealed no mutations among the study population. ConclusionRhodopsin mutations are scarcely associated with the autosomal recessive RP, suggesting that wide scale studies are needed to determine the genetic variations involved in RP and particularly in the autosomal recessive inheritance.

Diagnosis and clinical features of organic acidemias: A hospital-based study in a single center in Damascus, Syria

Background: Organic acidemias (OA) are a group of heterogeneous metabolic inherited disorders characterized by the accumulation of organic acids in body fluids and tissues. These are rare disorders and infrequently reported worldwide. In Syria, there is a lack of information regarding these disorders. Objective: Our hospital-based study aimed to describe the pattern of clinical and demographic presenting features of organic acidemias among Syrian children and to shed light on the diagnostic experience of organic acidemias in the Children's Hospital of Damascus through a five year period. Material and methods: We conducted a retrospective cohort study by reviewing the medical records of OA patients in the Children's Hospital of Damascus between 2008 and 2012. All cases were investigated by metabolic work up, including the acylcarnitine profile performed by tandem mass spectrometry (MS/MS) and quantitative urine organic acid analysis performed by gas chromatography mass spectrometry (GC-MS). Results: A total of 70 OA confirmed cases were included in the study. There were 46 males and 31 females. Twenty-seven cases were diagnosed after the first year of life. Methylmalonic acidemia was the most frequent disorder (57.1%). There were relatively high rates of family history of unexplained death and OA confirmed cases (50%), consanguinity (74.2%) and mortality (21.4%). The most frequent symptoms were apnea or respiratory distress (65.7%) and vomiting (40%). Conclusion: The lack of specific confirmatory diagnostic tests being performed and the high mortality and consanguinity rates among OA patients suggests high incidence of OA in Syria. Further studies are needed to determine the actual incidence of OA and the cost-effectiveness of applying a governmental mandatory newborn screening program.

Obesity susceptibility loci in Qataris, a highly consanguineous Arabian population

ObjectivesIn Qataris, a population characterized by a small size and a high rate of consanguinity, between two-thirds to three-quarters of adults are overweight or obese. We investigated the relevance of 23 obesity-related loci in the Qatari population.MethodsEight-hundred-four individuals assessed to be third generation Qataris were included in the study and assigned to 3 groups according to their body mass index (BMI): 190 lean (BMI < 25 kg/m2); 131 overweight (25 kg/m2 ≤ BMI < 30 kg/m2) and 483 obese (BMI ≥ 30 kg/m2). Genomic DNA was isolated from peripheral blood and genotyped by TaqMan.ResultsTwo loci significantly associated with obesity in Qataris: the TFAP2B variation (rs987237) (A allele versus G allele: chi-square = 10.3; P = 0.0013) and GNPDA2 variation (rs10938397) (A allele versus G allele: chi-square = 6.15; P = 0.013). The TFAP2B GG genotype negatively associated with obesity (OR = 0.21; P = 0.0031). Conversely, the GNDPA2 GG homozygous genotype associated with higher risk of obesity in subjects of age < 32 years (P = 0.0358).ConclusionWe showed a different genetic profile associated with obesity in the Qatari population compared to Western populations. Studying the genetic background of Qataris is of primary importance as the etiology of a given disease might be population-specific.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0459-3) contains supplementary material, which is available to authorized users.

Frequency of Congenital Anomalies in Newborns and Its Relation to Maternal Health in a Tertiary Care Hospital in Peshawar, Pakistan

Background: Congenital anomalies are a major cause of perinatal and neonatal deaths, both in low- and high-income countries. They are relatively common worldwide, affecting 3% to 5% of live births. Methods: A cross-sectional study was conducted from January 2014 to June 2014 at the Khyber teaching hospital in Peshawar. Specific patient information was obtained from patient records at the beginning of the study. Those individuals found to have at least one birth defect were approached and their attendants (mothers) were interviewed. Information regarding various risk factors was collected. Descriptive analyses were carried out. Results: Out of 1062 deliveries, 2.9% (31) of newborns had various congenital anomalies.b Hydrocephalus (22.6%), anencephaly (12.9%), and spina bifida (9.7%) were major anomalies. The maternal age ranged from 18 years to 46 years (mean: 30 ± 8). Most of the anomalies (35.5%) were present in the 26-30 years age group. Out of 31 babies, 6.4% had multiple anomalies. The preponderance of various congenital anomalies was seen in parity 1 (35.4%); parities 2 to 4 had lower incidences (35.4%). The consanguinity rate was 67.7%; only 32.3% of patients were using folic acid. History of passive smoking was positive in 16.1% of cases. Conclusion: Anencephaly and hydrocephalus were the most prominent anomaly detected; early prenatal diagnosis may be helpful in decreasing mortality by offering early termination. Low intake of folic acid and a high consanguinity rate were the most common associated risk factors for congenital anomalies. These risk factors may be reduced by creating awareness regarding the avoidance of consanguineous marriage and promoting the use of folic acid during pregnancy.