scholarly journals Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India

2021 ◽  
Author(s):  
Rajat Hegde ◽  
Smita Hegde ◽  
Suyamindra S. Kulkarni ◽  
Aditya Pandurangi ◽  
Pramod B. Gai ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Genetic Analysis ◽  
Missense Mutation ◽  
Mentally Ill ◽  
Large Population ◽  
Original Structure ◽  
Male Predominance ◽  
Local Configuration ◽  
Autistic Population

Abstract Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population. Aim The present study hypothesizes that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [NLGN4Y] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India. Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid. Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [NLGN4Y] gene especially in the male predominance of autism in Indian autistic population.

scholarly journals Molecular Analysis of Prothrombotic Gene Variants in Patients with Acute Ischemic Stroke and with Transient Ischemic Attack

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 723
Author(s):  
Gustavo Cernera ◽  
Marika Comegna ◽  
Monica Gelzo ◽  
Marcella Savoia ◽  
Dario Bruzzese ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Causes Of Death ◽  
Southern Italy ◽  
Large Population ◽  
Mthfr C677t ◽  
Geographic Area ◽  
Gene Variants ◽  
Interesting Possibility ◽  
Ischemic Attack

Background and objectives: ischemic stroke (IS) is among the most frequent causes of death worldwide; thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk subjects. Materials and Methods:we tested nine variants in genes involved in thrombotic pathway in 282 patients that experienced IS and 87 that had transient ischemic attacks (TIA) in comparison to 430 subjects from the general population (GP) of the same geographic area (southern Italy). We included cases of young and child IS to evaluate the eventual differences in the role of the analyzed variants. Results: we did not observe significant differences between TIA and the GP for any of the variants, while the allele frequencies of methylene-tetrahydrofolate reductase (MTHFR) C677T, beta-fibrinogen -455G>A and factor (FXIII) V34L were significantly higher in patients with IS than in the subjects from the GP. No significant interaction was observed with sex. Conclusions: the present data argue that some gene variants have a role in IS and this appears to be an interesting possibility to be pursued in large population studies to help design specific strategies for IS prevention.

scholarly journals A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eder Gambeta ◽  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
Gerald W. Zamponi
Keyword(s):  
Trigeminal Neuralgia ◽  
Missense Mutation ◽  
Neurotransmitter Release ◽  
Trigeminal System ◽  
Wild Type ◽  
Calcium Dependent ◽  
Whole Cell Patch Clamp ◽  
C Terminus ◽  
Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

scholarly journals Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo

2021 ◽  
Author(s):  
Dorothy Benton ◽  
Eva C Jaeger ◽  
Arielle Kilner ◽  
Ashley Kimble ◽  
Josh Lowry ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Oocyte Maturation ◽  
Protective Role ◽  
C Elegans ◽  
Direct Target ◽  
The One ◽  
Actomyosin Cytoskeleton ◽  
Embryonic Viability ◽  
Anterior Posterior

Abstract Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. While the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. While depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.

scholarly journals The Role of Intuition and Prognostic Risk Assessment Regarding the Leave of Offenders with Mental Disorders

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. Schmitt
Keyword(s):  
Risk Assessment ◽  
Mentally Ill ◽  
Psychological Factors ◽  
Methodological Problem ◽  
German Law ◽  
Decision Makers ◽  
Mentally Ill Offenders ◽  
Rare Occurrence ◽  
German State

The granting of leave during terms of imprisonment plays an important part in the treatment of mentally ill offenders. According to German law, leave is to be granted in those cases where the abuse of this privilege or an attempt to flee can be negated. These regulations also, however, imply that the risk assessment of a patient's offence-related recidivism can not be the only criterion for the granting of leave.So far, there have only been few studies about the prognostic risk assessment of the general abuse of leave. This is rather astonishing, as the granting of leave outside the institutional grounds, in particular, is a decision which often leaves those responsible fraught with anxiety. Furthermore, the abuse of a granted temporary release can lead to severe consequences on various levels.As part of a study to be conducted in the German state of Rhineland-Palatinate, decisions about granting leave are to be analyzed and possible predictors of the abuse of leave are to be examined.It is assumed that the abuse of leave is likely to be motivated by the conditions of particular situations and can primarily be explained by normal psychological factors.However, it should be pointed out that, as the abuse of leave is such a rare occurrence, it poses a significant methodological problem. The criterion to be examined therefore needs to be exactly defined and particular attention must be paid to achieve an adequately high interreliability of the decision makers.

scholarly journals Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel missense mutation in AVP gene in a large Italian kindred

Endocrine ◽  
2021 ◽  
Author(s):  
Carlotta Marzocchi ◽  
Silvia Cantara ◽  
Alfonso Sagnella ◽  
Maria Grazia Castagna ◽  
Marco Capezzone
Keyword(s):  
Diabetes Insipidus ◽  
Missense Mutation ◽  
Autosomal Dominant ◽  
Three Dimensional ◽  
Rare Condition ◽  
Central Diabetes Insipidus ◽  
Disulfide Bridges ◽  
Italian Family ◽  
Avp Gene

Abstract Purpose Familial neurohypophysial diabetes insipidus (FNDI), commonly caused by autosomal dominant arginine vasopressin (AVP) mutations, is a rare condition in which vasopressin fails in regulating body’s level of water with final polyuria and polydipsia. Genetic testing in familial cases of FNDI should be carry out to ensure adequate treatments and avoid disease manifestations especially in infants. Methods In this study, we investigated three-generations of a large Italian family with clinical diagnosis of familial central diabetes insipidus for the presence of potential pathogenic mutations in the AVP gene. Results We identified a heterozygous missense mutation (c.154 T > A; p.C52S) in AVP gene in all affected members studied of a large Italian family. In silico tools were used to investigate the pathogenic role of the mutation and three-dimensional protein structure predicted that the p.C52S impairs disulfide bridges formation resulting in misfolding of the protein. Conclusions This is the first study that identified a novel missense p.C52S mutation as causative of central diabetes insipidus in a large Italian pedigree.

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