Early Development of Newborn Screening for HCU and Current Challenges

Classic homocystinuria (HCU) was added to newborn screening (NBS) by Robert Guthrie a few years after the disorder was first described. The justification for NBS was similar to that for PKU, that presymptomatic identification and early dietary treatment would prevent the clinical consequences, which, for HCU, are mental deficiency, ectopia lentis, skeletal abnormalities, and thromboembolism. It was assumed that identifying increased methionine in the screening blood specimen would identify all affected neonates. However, it is now clear that many with HCU are missed by NBS, mainly because the methionine level in the first days of life is normal or below the cutoff level in the NBS program. This includes virtually all of those with B6-responsive HCU. Thus, a more effective method of NBS for HCU should be considered. Included among the possibilities are decreasing the methionine cutoff level, requiring an increase in the Met/Phe ratio if the methionine level is not at or greater than the cutoff level, using methionine as the primary screen with homocysteine as a second-tier test, or replacing methionine with homocysteine as the primary screen. Homocysteine is the primary metabolite that increases in HCU, while the methionine increase is secondary, so homocysteine is usually increased before the increase in methionine, almost always during the first few days of life. Finally, targeted gene screening might be considered. All of these possibilities would impose added expense and labor to NBS, so meeting these challenges would likely require a regional or national effort.

A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies

Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. The syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G > T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome.

Familial SYN1 variants related neurodevelopmental disorders in Asian pediatric patients

Background SYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years. Methods In the study, we reported two male patients with familial SYN1 variants related neurodevelopmental disorders from Asian population. Previously published cases with significant SYN1 variants from the literature were also included to analyze the phenotype and genotype of the disorder. Results Two maternally inherited SYN1 variants, including c.C1076A, p.T359K in proband A and c.C1444T, p. Q482X in proband B (NM_133499) were found, which have never been described in detail. Combining with our research, all reported probands were male in the condition, whose significant SYN1 variants were inherited from their asymptomatic or mild affected mother. Although the disorder encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, patients’ clinical manifestations vary in genders and individuals, even in the same pedigree. Conclusion We firstly reported two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Gender and phenotype differences should be highly valued in the disorder.

FXS-causing missense mutations disrupt FMRP-containing neuronal granule formation, dynamics, and function

Fragile X Syndrome (FXS) is the most prevalent cause of inherited mental deficiency and is the most common monogenetic cause of autism spectral disorder (ASD). Here, we demonstrate that disease-causing missense mutations in the conserved K homology (KH) RNA binding domains (RBDs) of FMRP cause defects in its ability to form RNA transport granules in both cells and neurons. Using molecular, genetic, and imaging approaches in the Drosophila FXS model system, we show that the KH1 and KH2 domains of FMRP regulate distinct aspects of neuronal FMRP granule formation, dynamics, and transport. Furthermore, mutations in both KH domains disrupt translational repression in cells and the localization of known FMRP target mRNAs in neurons. These results suggest that the KH domains play an essential role in neuronal FMRP granule formation and function. Dysregulation of these processes may be linked to FXS.

Familial SYN1 Pathogenic Mutations Related Neurodevelopmental Disorders in Asian Pediatric Patients

Background: SYN1 encodes synapsin I, which is a neuronal phosphoprotein in relation to the membranes of small synaptic vesicles. Pathogenic variants in the gene have been confirmed as genetic causes of neurodevelopmental disorders. Methods: In our study, we collected clinical information of two male probands with intellectual disability, and performed whole exome sequencing on both patients and their parents. We also reviewed more SYN1 variant cases in pervious publications.Results: Two maternally inherited variants in SYN1 gene (NM_133499:c.C1076A (p.T359K) in proband A and NM_133499:c.C1444T (p. Q482X) in proband B) were found in our patients, which have never been described in detail before. After a literature review, we found that all probands have been reported so far were male, who inherited the significant SYN1 variants from their asymptomatic or mild affected mother. Although the disease encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, the phenotypes of family members vary in gender.Conclusion: Here, we firstly report two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Our results supported that gender and phenotype differences should be highly valued in this disorder.

Formation of scientific notions in students with mental deficiency

The article briefly presents a didactic research that analyzes the formation and introduction of scientific notions specific to Chemistry through active-participatory methods for obtaining higher school results, triggering students' interest, active involvement in their own training, thus ensuring the optimization of the teaching and learning chemistry to students with mental disabilities in special school. The fundamental objective of the research was to demonstrate the importance of active-participatory methods in the formation of notions in the Sciences curricular area in general, respectively in the discipline of Chemistry in particular, where the student becomes an active participant in his own training. Through active-participatory methods used in the process of learning, recovery and socialization of the mentally handicapped, it becomes possible to achieve the fundamental objectives of acquiring knowledge, to accelerate students’ work pace, bring the class working together and train as many students as possible during the lessons. During the activities based on interactive methods organized in groups, it was found that the students modeled their behavior, the spirit of organization increased being more orderly and more involved in solving the work tasks received; interpersonal relationships and cooperation between students have improved (better students help their colleagues to understand the notions taught, this fact leading to an increase in their own results).

Answer Selection Process and Error Detection when Solving Simple Cognitive Tasks

The study is aimed at examining the process of erroneous and correct answers when solving simple cognitive tasks of the same type in the group of adolescents with normal intelligence and those with mild mental deficiency. To study the nature of making errors the author studied factors influencing the process of answer selection, such as conditions of stimulus presentation, stimuli categorical congruence, and unconscious error detection markers of various kinds. The study revealed that if adolescents with normal intelligence make mistakes they do it trying to do the task quickly, while adolescents with mild mental deficiency make mistakes because of the task difficulty and demonstrate a low level of mindfulness of making a mistake, and slow-up adjustment process after a correct answer. Depending on whether there being or not being mental deficiency, certain differences in the process of error detection and the influence of conditions of stimulus presentation were detected.