Recent Advances in Autism Spectrum Disorders: Applications of Whole Exome Sequencing Technology

Autism spectrum disorders (ASD) is characterized by three core symptoms with impaired reciprocal social interaction and communication, a pattern of repetitive behavior and/or restricted interests in early childhood. The prevalence is higher in male children than in female children. As a complex neurodevelopmental disorder, the phenotype and severity of autism are extremely heterogeneous with differences from one patient to another. Genetics has a key role in the etiology of autism. Environmental factors are also interacting with the genetic profile and cause abnormal changes in neuronal development, brain growth, and functional connectivity. The term of exome represents less than 1% of the human genome, but contains 85% of known disease-causing variants. Whole-exome sequencing (WES) is an application of the next generation sequencing technology to determine the variations of all coding regions, or exons of known genes. For this reason, WES has been extensively used for clinical studies in the recent years. WES has achieved great success in the past years for identifying Mendelian disease genes. This review evaluates the potential of current findings in ASD for application in next generation sequencing technology, particularly WES. WES and whole-genome sequencing (WGS) approaches may lead to the discovery of underlying genetic factors for ASD and may thereby identify novel therapeutic targets for this disorder.

mRNA Expression Level of Interleukin Genes in the Determining Phases of Behcet's Disease

BACKGROUND: Behcet's disease (BD), first described in 1937 as a triadic complex of symptoms (oral aphthae, genital ulcers, and hypopyon uveitis), is a chronic, relapsing, multisystemic idiopathic inflammatory disease. OBJECTIVE: The objective of this study was to investigate the usability of messenger RNA (mRNA) expression of cytokine genes for following up patients with BD and also assess polymorphisms in these genes as to how they influence mRNA expression. METHODS: This study investigated the role of the IL1A -889(C/T), IL1B -511(C/T), and IL2 -330(T/G) polymorphisms by polymerase chain reaction (PCR)-restriction fragment length polymorphisms and the expression levels of the genes by real-time PCR in BD. RESULTS: The frequency of the IL2 -330 G allele was found to be significantly higher in patients with BD. A decreased level of IL1A gene expression was found in the patient group with clinically active BD compared to controls. Increased IL1B gene expression levels werefound in patient groups with active, inactive, or ocular BD (p<0.001). IL2 gene expression level manifested no significant change compared to controls in the patient group with clinically active BD; it increased in the groups with clinically inactive BD or ocular involvement. CONCLUSION: IL1A, IL1B, and IL2 gene expression, and IL2 promoter polymorphisms, may be valuable markers for predicting risk in the development of BD. We believe that the results reveal the importance of achieving a better understanding of BD and the prospects of developing future therapeutic strategies.

molecular analysis of familial Mediterranean fever disease in a cohort of Turkish patients

Familial Mediterranean fever [FMF] is an autosomal recessive disorder caused by mutations in MEFV gene, which encodes pyrin. FMF is especially prevalent among Turks, Armenians, non-Ashkenazi Jews, and Arabs. The aim of this study was to determine the frequency and spectrum of 12 MEFV mutations of these patients and any genotype-phenotype correlation in this large Turkish group. A retrospective study at Erciyes University Medical Faculty, from January 2007 to June 2009. We enrolled 446 Turkish FMF patients and identified the known 12 MEFV mutations with clinical investigations. DNA was amplified by PCR and subjected to reverse hybridization for the detection of MEFV gene mutations. Among the 446 patients, 103 [46.6%] had a heterozygous genotype, 44 [19.9%] had a homozygous genotype, and 74 [33.49%] had a compound heterozygous genotype. The most common mutation detected was heterozygote M694V [46/221]. Of the included 446 patients, 218 [48.87%] were male and 228 [51.12%] were female. High parental consanguinity rates affect FMF development. The clinical spectrum varied with different mutation profiles. This study plays an important role in detecting the distribution of MEFV mutations and determining clinical approaches among Turk FMF patients. Also, we seemed to detect a distinctive clinical picture, specifically a lower frequency of amyloidosis

Prenatal diagnosis of unique translocation t[7;15] [q11.23;q26.3] in a fetus

Translocation, as the name implies, is the movement of a chromosomal segment to a new location in the genome. Once a structural chromosome abnormality has been detected, prenatal diagnosis in subsequent pregnancies and termination of pregnancy in the case of an unbalanced fetal karyotype is recommended. A woman was referred at 18 weeks of gestation to the Medical Genetics Clinic for an amniocentesis because of advanced maternal age [35], triple test risks and recurrent abortions. Prenatal ultrasound was normal. The amniocentesis revealed a male karyotype with an apparently balanced translocation:46, XY, t[7;15] [q11.23; q26.3]. To our knowlegde, this is the first case in the literature of prenatal diagnosis of the unique translocation t[7;15] [q11.23;q26.3] in a fetus.