Autism Spectrum Disorder - A Complex Genetic Disorder

Autism spectrum disorder is an entity that reflects a scientific consensus that several previously separated disorders are actually a single spectrum disorder with different levels of symptom severity in two core domains - deficits in social communication and interaction, and restricted repetitive behaviors. Autism spectrum disorder is diagnosed in all racial, ethnic and socioeconomic groups and because of its increased prevalence, reported worldwide through the last years, made it one of the most discussed child psychiatric disorders. In term of aetiology as several other complex diseases, Autism spectrum disorder is considered to have a strong genetic component

Clinical characteristics, disease evolution and survival in patients with chronic myeloid leukemia, BCR-ABL1 (+) and T315I mutation.

Introduction: The T315I mutation in patients with chronic myeloid leukemia (CML) has been associated with therapeutic resistance and an unfavourable prognosis.Aim: To study the frequency of T315I mutation in patients with CML, BCR-ABL (+), their clinical characteristics, disease evolution, and median survival.Patients and methods: We studied 75 patients with CML and BCR-ABL1 (+). T315I mutation was detected by digital droplet PCR and BCR-ABL1 was analyzed by RT-PCR. A comparative analysis was performed by sex, age, disease phase, risk group, treatment, molecular response (MR), and median survival in T315I (+) and T315I (−) patients.Results: T315I mutation was detected in 11 patients (14.7%). No significant difference was found in the phase, risk group, and first-line therapy. A significantly higher proportion of T315I (+) did not achieve MR >3.5 log: 8 (72.7%) vs. 22 (34.4%) (p=0.023). The lowest mean BCR-ABL1 levels were significantly higher in the CML T315I (+) group compared to the CML T315I (−) group: 12.1±6.0 vs. 3.77±1.28 (p=0.009). The median survival of T315I (+) patients was significantly shorter: 73 months vs. 175 months (p<0.0001, CI 95%).Conclusions: Our data confirm the world experience on the frequency of T315I mutation, including the unfavourable evolution, resistance to TKI treatment and short survival. ddPCR is a highly sensitive method for early detection of genetic mutations which gives the chance for effective treatment

Blood-Based Gene Expression in children with Autism spectrum disorder

Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although numerous autism susceptible genes were identified, the etiology of autism is not fully explained. The study aimed to examine gene expression profiling in peripheral blood from 60 individuals divided into two groups: children with ASD and age- and gender-matched healthy subjects (ASD control). A genome-wide sequencing of copy DNA molecules was conducted to obtain information for quantitative expression of all genes subject to this study and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis was used to further understand genes’ biological functions. Based on the conducted expression analysis 23 differentially expressed genes and 21 KEGG signaling pathways with statistical significant change were identified. Blood-based comparative gene expression profiling analysis is useful in discovering genetic markers associated with ASD. Our data will provide a valuable resource for discovery purposes and for comparison to other gene expression-based, genome-wide studies and other functional data

An analysis and evaluation of the correlation between DNA polymorphism in the genes MTHFR, PAI-1 and serum creatinine, creatinine clearance and albumin/creatinine ratio in morning urine of patients with type 2 diabetes mellitus and diabetic nephropathy.

Introduction: Diabetic nephropathy is a major microangiopathic complication of type 2 diabetes and a leading cause of chronic kidney disease (CKD).Aim: To improve the diagnostic approach to early diagnosis of diabetic nephropathy in patients with type 2 diabetes mellitus.Materials and methods: One hundred fifty patients were divided into three groups. Group 1 consisted of 67 patients with type 2 diabetes mellitus (DM2) and diabetic nephropathy with stage 1 or 2 of CKD. Group 2 included 45 patients with DM2 without clinical and laboratory evidence for diabetic nephropathy. Group 3 had 38 healthy individuals. The polymorphism of the MTHFR C677T and PAI14G/5G gene was determined by extracted genomic DNA from peripheral blood cells. All patients underwent a real-time PCR reaction. Serum creatinine, MDRD creatinine clearance, albumin/creatinine ratio were examined.Results: The correlation analysis we performed showed a very strong correlation of serum creatinine, creatinine clearance and albumin/ creatinine ratio with the C677T polymorphism of the MTHFR gene and the 4G/5G polymorphism of the PAI-1 gene. We used descriptive statistics, ANOVA, and multiple comparisons; the level of significance was set at p&amp;lt;0.05.Conclusions: 1. The presence of the T allele in the MTHFR gene determines the tendency to increase serum creatinine, decrease creatinine clearance, and increase the albumin/creatinine ratio in morning urine; 2. The presence of 4G allele in the PAI-1 gene determines the tendency to increase serum creatinine, decrease creatinine clearance, and increase the albumin/creatinine ratio in morning urine

A de novo microdeletion 2p24.3-25.1 identified in a girl with global development delay

Interstitial microdeletions of the distal 2p are very rare. A small number of cases have been reported in the literature, involving regions 2p23-p25, 2p23-p24 and 2p24-p25. The most common symptoms involve: intrauterine growth retardation, developmental delay, mental retardation, microcephaly, craniofacial anomalies, musculoskeletal abnormalities, congenital heart defect and hearing impairment. Herein we report on a Caucasian girl, born after in vitro fertilization with discrete facial dysmorphism, growth failure, borderline neurodevelopment and congenital heart defect. A de novo pericentric inversion of chromosome 2 was identified by routine karyotyping. An interstitial microdeletion of 2p24.3p25.1 was found by array karyotyping and following FISH analysis revealed that the deletion affects the inverted chromosome 2. This case illustrates the utility of high resolution methods to identify submicroscopic quantitative changes in structurally rearranged chromosomes. The precise determination of the genetic content of small quantitative changes in the genome provides important information for genetic counseling, enabling to predict the course of disease and the planning of adequate therapy and prophylaxis in affected families

Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children

Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population.The clinical phenotype of the twenty R446* homozygotes was relatively homogeneous, with lactic acidosis crisis in the first days or months of life as the most common initial presentation (15/20 patients) and delayed psychomotor development and/or seizures in infancy as the leading manifestations in a smaller group (5/20 patients). The subsequent clinical picture was dominated by impaired physical growth and a very consistent pattern of static cerebral palsy-like encephalopathy with spasticity and severe to profound mental retardation seen in over 80% of cases. Most patients had a positive family history.We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis. It will facilitate and accelerate diagnosis in a large proportion of cases, allow early rehabilitation to alleviate the chronic clinical course, and prevent further affected births in high-risk families