Genetic Research on Neurodevelopmental Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 6777

Special Issue Editor


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Guest Editor
1. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
2. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Interests: human genetics; neuroscience; neurodevelopmental disorders; whole genome sequencing; whole exome sequencing; molecular diagnostics; genetic counselling; premerital genetic testing

Special Issue Information

Dear Colleagues,

Neurodevelopmental disorders stand as one of the most frequent human genetic disorders. The recent advances in technologies and generating and analyzing high throughput sequencing data have exponentially increased the rate of molecular diagnostics.

The findings from genetic studies help to pinpoint potential therapeutic targets, identify informative biomarkers, and design effective preventive strategies. Precise and intime molecular diagnostics is a key to patient management and adopting the right plan for theraputics.

In this Special Issue, we encourage authors to submit their work related to neurodevelopmental disorders caused either by single or multiple genes, analyzed for whole genome, whole exome, genome-wide genotyping, or clinical diagnosis using advanced technologies in imaging, or developing advanced tools for the analysis of genomics, transcriptomics, proteomics, or metabolomics. The scope of this Issue is not limited to novel gene or causative variants identification; it also covers premarital testing testing, non-invasive prenatal testing (NIPT), and new born screening.

Dr. Muhammad Imran Naseer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • rare neurodevelopmental disorders
  • SNP microarray
  • whole genome sequencing
  • whole exome sequencing
  • molecular diagnostics
  • genetic counselling
  • premarital genetic testing
  • epigenetics
  • complex diseases
  • genetic disorders
  • skeletal deformities

Published Papers (4 papers)

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10 pages, 1624 KiB  
Article
Homozygous Duplication in the CHRNE in a Family with Congenital Myasthenic Syndrome 4C: 18-Year Follow Up
by Ahmad M. Almatrafi, Majed M. Alluqmani and Sulman Basit
Biomedicines 2023, 11(11), 2983; https://doi.org/10.3390/biomedicines11112983 - 6 Nov 2023
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Abstract
Background and objectives: Congenital myasthenic syndromes (CMSs) are rare inherited diseases characterized by muscle weakness and fatigability on exertion resulting from defects in the neuromuscular junctions. Mutations in 32 genes have been reported as the underlying causes of CMS, with mutations in the [...] Read more.
Background and objectives: Congenital myasthenic syndromes (CMSs) are rare inherited diseases characterized by muscle weakness and fatigability on exertion resulting from defects in the neuromuscular junctions. Mutations in 32 genes have been reported as the underlying causes of CMS, with mutations in the cholinergic receptor nicotinic epsilon subunit (CHRNE) being the most common cause of the disease. Methodology and Materials: This study investigated a large consanguineous family with multiple individuals suffering from abnormal fatigue and muscle weakness in the ocular and limb regions. Moreover, the affected individuals were followed up for 18 years to observe the clinical course of the disease. Results: High-quality exome sequencing followed by bidirectional Sanger sequencing revealed a homozygous duplication variant (NM_000080.4: c.1220-8_1227dup) in the splice acceptor site of exon 11 of the CHRNE gene. This variant is predicted to cause frameshift and premature termination (p.Cys410ProfsTer51). Both parents had heterozygous duplication variants with no clinical symptoms. The personalized treatment of the affected individuals resulted in a marked improvement in the clinical symptoms. More than 80% of the disease symptoms in the affected individuals subsided after the use of pyridostigmine and salbutamol (4 mg). Conclusions: This is the first report of long-term follow up of cases with homozygous insertion (c.1220-8_1227dup) in the CHRNE gene. Furthermore, this report expands the phenotypic symptoms associated with the CHRNE mutation. Full article
(This article belongs to the Special Issue Genetic Research on Neurodevelopmental Disorders)
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21 pages, 1153 KiB  
Article
Insight into Genetic Mutations of SZT2: Is It a Syndrome?
by Osama Y. Muthaffar, Mohammed M. S. Jan, Anas S. Alyazidi, Taif K. Alotibi and Eman A. Alsulami
Biomedicines 2023, 11(9), 2402; https://doi.org/10.3390/biomedicines11092402 - 28 Aug 2023
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Abstract
Background: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in [...] Read more.
Background: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene could result in hyperactive mTORC1 signaling, which can lead to several neurological disorders. Aim of the study: To review every reported case and present two novel cases to expand the current knowledge and understanding of the mutation. Methods: Whole exome sequencing (WES) was used to identify the novel cases and present their clinical and radiological findings. A detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data were extracted. Results: The study included 16 female patients and 13 male patients in addition to the 2 novel male cases. Eighteen patients had heterozygous mutations; others were homozygous. The majority presented with facial dysmorphism (n = 22). Seizures were noted as the predominant hallmark (n = 26). Developmental delay and hypotonia were reported in 27 and 15 patients, respectively. The majority of patients had multifocal epileptiform discharges on the electroencephalogram (EEG) and short and thick corpus callosum on the magnetic resonance imaging (MRI). Conclusion: Several promising features are becoming strongly linked to patients with SZT2 mutations. High variability among the cases was observed. Developmental delay and facial dysmorphism can be investigated as potential hallmarks; aiding clinicians in diagnosing the condition and optimizing management plans. Full article
(This article belongs to the Special Issue Genetic Research on Neurodevelopmental Disorders)
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14 pages, 1162 KiB  
Article
Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan
by Murad Ali Rahat, Fazal Akbar, Akhtar Rasool, Muhammad Ilyas, Allah Rakha, Sulaiman Shams, Musharraf Jelani, Fehmida Bibi, Bader H. Shirah, Angham Abdulrhman Abdulkareem, Muhammad Imran Naseer and Muhammad Israr
Biomedicines 2023, 11(4), 1228; https://doi.org/10.3390/biomedicines11041228 - 20 Apr 2023
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Abstract
The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the [...] Read more.
The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the Malakand Division. Methods: Eye colour digital photographs and buccal swab samples of 893 individuals of different age groups were collected. Multiplexed SNaPshot single base extension chemistry was used, and the genotypic results were analysed. Snapshot data were used for eye colour prediction through the IrisPlex and FROG-kb tool. Results: The results of the present study found brown eye colour to be the most prevalent eye colour in comparison to intermediate and blue coloured. Overall, individuals with brown-coloured eyes possess CT (46.84%) and TT (53.16%) genotypes. Blue eye-coloured individuals are solely of the CC genotype, while individuals of intermediate eye colour carry CT (45.15%) and CC (53.85%) genotypes in rs12913832 SNP in the HERC2 gene. It was also revealed that brown-coloured eyes individuals were dominant among all age groups followed by intermediate and blue. Statistical analysis between particular variables and eye colour showed a significant p-value (<0.05) for rs16891982 SNP in SLC45A2 gene, rs12913832 SNP in HERC2 gene, rs1393350 SNP in SLC45A2, districts and gender. The rest of the SNPs were non-significant with eye colour, respectively. The rs12896399 SNP and SNP rs1800407 were found significant with rs16891982 SNP. The result also demonstrated that the study group differs from the world population based on eye colour. The two eye colour prediction results were compared, and it was discovered that IrisPlex and FROG-Kb had similar higher prediction ratios for Brown and Blue eye colour. Conclusions: The results of the current study revealed brown eye colour to be the most prevalent amongst members of the local population of Pakhtoon ethnicity in the Malakand Division of northern Pakistan. A set of contemporary human DNA samples with known phenotypes are used in this research to evaluate the custom panel’s prediction accuracy. With the aid of this forensic test, DNA typing can be supplemented with details about the appearance of the person from whom the sample was taken in cases involving missing persons, ancient human remains, and trace samples. This study may be helpful for future population genetics and forensics studies. Full article
(This article belongs to the Special Issue Genetic Research on Neurodevelopmental Disorders)
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8 pages, 260 KiB  
Commentary
DAT1 5′-Un-Translated-Region Methylation Patterns as Bio-Markers of ADHD Psycho-Pathology: Contribution to Disease Prognosis and to Monitoring of a Successful Therapy
by Valentina Carpentieri, Silvia Cugno, Katarina Lockic, Esterina Pascale and Walter Adriani
Biomedicines 2023, 11(9), 2546; https://doi.org/10.3390/biomedicines11092546 - 15 Sep 2023
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Abstract
Epigenetic modifications, such as changes in DNA methylation, have been linked to several diseases in recent years. The purpose of our study was to search for biomarkers that (using non-invasive techniques) could assist the clinician in the prognosis of infant/adolescent psychopathology. We previously [...] Read more.
Epigenetic modifications, such as changes in DNA methylation, have been linked to several diseases in recent years. The purpose of our study was to search for biomarkers that (using non-invasive techniques) could assist the clinician in the prognosis of infant/adolescent psychopathology. We previously showed that changes in methylation of the 5’-UTR in the DAT1/SLC6A3 gene can be used as a biomarker for the prognosis of initial severe ADHD: treatment-resistant severe ADHD children were characterized by methylated CpG 1 in particular, while methylated CpGs 2 and 6 were then found in children who improved after the therapy. Further, we confirmed these outcomes and provided the hypothesis that symptomatology might be influenced by the children’s genotype and family environment. In particular, levels of CpG 3 methylation in the heterozygous ADHD children were associated with high paternal own risk or stress. Eventually, we found that the same biomarkers are more broadly useful in the field of internalizing or externalizing symptoms (when a certain vulnerability is already present in the child). In particular, it was seen how inheriting specific 9-repeat or 10-repeat VNTR alleles from the mother or from the father could modify the pattern of methylation at the 5′-UTR of the DAT1 gene. A specific pattern of methylations (with CpG 2 following either CpGs 1 + 3 or CpG 6 at the DAT1 5′-UTR) has been associated, therefore, with the likelihood of an internalizing or externalizing developmental trajectory entailing ADHD-like psycho-pathological characteristics. Since each individual responds differently to a specific treatment, we suggest that these methylation patterns may be used as biomarkers to monitor the outcome and/or predict the success of a given therapy (personalized medicine). Full article
(This article belongs to the Special Issue Genetic Research on Neurodevelopmental Disorders)
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