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13 pages, 29065 KiB

Open AccessArticle

Whole Exome Sequencing Identifies a Novel Homozygous Missense Mutation in the CSB Protein-Encoding ERCC6 Gene in a Taiwanese Boy with Cockayne Syndrome

by Ching-Ming Lin, Jay-How Yang, Hwei-Jen Lee, Yu-Pang Lin, Li-Ping Tsai, Chih-Sin Hsu, G. W. Gant Luxton and Chih-Fen Hu

Life 2021, 11(11), 1230; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111230 - 14 Nov 2021

Cited by 2 | Viewed by 1782

Abstract

Background: Cockayne syndrome (CS) is a rare form of dwarfism that is characterized by progressive premature aging. CS is typically caused by mutations in the excision repair cross-complementing protein group 6 (ERCC6) gene that encodes the CS group B (CSB) protein. [...] Read more.

Background: Cockayne syndrome (CS) is a rare form of dwarfism that is characterized by progressive premature aging. CS is typically caused by mutations in the excision repair cross-complementing protein group 6 (ERCC6) gene that encodes the CS group B (CSB) protein. Using whole exome sequencing, we recently identified a novel homozygous missense mutation (Leu536Trp) in CSB in a Taiwanese boy with CS. Since the current database (Varsome) interprets this variant as likely pathogenic, we utilized a bioinformatic tool to investigate the impact of Leu536Trp as well as two other variants (Arg453Ter, Asp532Gly) in similar articles on the CSB protein structure stability. Methods: We used iterative threading assembly refinement (I-TASSER) to generate a predictive 3D structure of CSB. We calculated the change of mutation energy after residues substitution on the protein stability using I-TASSER as well as the artificial intelligence program Alphafold. Results: The Asp532Gly variant destabilized both modeled structures, while the Leu536Trp variant showed no effect on I-TASSER’s model but destabilized the Alphafold’s modeled structure. Conclusions: We propose here the first case of CS associated with a novel homozygous missense mutation (Leu536Trp) in CSB. Furthermore, we suggest that the Asp532Gly and Leu536Trp variants are both pathogenic after bioinformatic analysis of protein stability. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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11 pages, 452 KiB

Open AccessArticle

Lactate Predicts Neurological Outcomes after Perinatal Asphyxia in Post-Hypothermia Era: A Prospective Cohort Study

by Yi-Fang Tu, Po-Ming Wu, Wen-Hao Yu, Chung-I Li, Cheng-Lin Wu, Lin Kang, Yung-Chieh Lin, Hsin-I Shih and Chao-Ching Huang

Life 2021, 11(11), 1193; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111193 - 05 Nov 2021

Cited by 4 | Viewed by 1684

Abstract

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality and neurological disability in infancy after perinatal asphyxia. Reliable biomarkers to predict neurological outcomes of neonates after perinatal asphyxia are still not accessible in clinical practice. Methods: A prospective cohort study [...] Read more.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality and neurological disability in infancy after perinatal asphyxia. Reliable biomarkers to predict neurological outcomes of neonates after perinatal asphyxia are still not accessible in clinical practice. Methods: A prospective cohort study enrolled neonates with perinatal asphyxia. Biochemical blood tests and cerebral Doppler ultrasound were measured within 6 h of age and at the 4th day old. Neurological outcomes were assessed at 1 year old. Results: Sixty-four neonates with perinatal asphyxia were enrolled. Fifty-eight (90%) had hypoxic-ischemic encephalopathy (HIE) including 20 (34%) Stage I, 21 (36%) Stage II, and 17 (29%) Stage III. In the asphyxiated infants without therapeutic hypothermia, HIE stage, PH, and base excess levels within 6 h of age were the predictors of adverse outcomes. In the asphyxiated infants receiving therapeutic hypothermia, HIE stage failed to predict outcomes. Instead, blood lactate levels and pulsatility index (PI) of medial cerebral arteries (MCA) either in 6 h of age or at the 4th day old independently predicted adverse outcomes. Conclusions: Blood lactate, which is a common accessible test at the hospital and MCA PI on cerebral ultrasound could predict adverse outcomes in asphyxiated infants receiving therapeutic hypothermia. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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10 pages, 1156 KiB

Open AccessArticle

High Risk for Attention-Deficit Hyperactive Disorder in Children with Strabismus: A Nationwide Cohort Study from the National Health Insurance Research Database

by Chia-Ying Tsai, Chien-Chia Su, Yao-Lin Liu, I-Ju Tsai and Tzu-Hsun Tsai

Life 2021, 11(11), 1139; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111139 - 26 Oct 2021

Cited by 4 | Viewed by 2836

Abstract

Strabismus is associated with amblyopia and a lower quality of life. Attention-deficit hyperactivity disorder (ADHD) is common among children and adolescents, and influences their academic, vocational, and social life. Previous studies have suggested an association between strabismus and ADHD. Using data from the [...] Read more.

Strabismus is associated with amblyopia and a lower quality of life. Attention-deficit hyperactivity disorder (ADHD) is common among children and adolescents, and influences their academic, vocational, and social life. Previous studies have suggested an association between strabismus and ADHD. Using data from the Taiwan National Health Insurance Research Database between 2000 and 2010, we performed a large-scale cohort study comparing the incidence, risk factors, and severity of ADHD in children with and without strabismus. A total of 2049 patients <18 years old with newly diagnosed strabismus (esotropia: 404; exotropia: 1645) were identified, and 8196 age- and sex-matched controls without strabismus were also included. After an average of 6.5 ± 2.9 years of follow-up, the incidence of ADHD per 1000 person-years was 5.39 in the strabismus group (esotropia: 9.93; exotropia: 4.11) and 3.23 in the control group. The cumulative incidence of ADHD was significantly greater in the esotropia (hazard ratio [HR]: 2.04; 95% confidence interval [CI]:1.36–3.06; p = 0.0007) and exotropia groups (HR: 1.44; 95% CI: 1.03–2.03; p = 0.038) than in the controls. Patients with strabismus had more comorbidities than those without (p < 0.05). In summary, this large-scale study found a higher cumulative incidence of ADHD in patients with strabismus, especially in those with esotropia. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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10 pages, 966 KiB

Open AccessArticle

Is Preterm Birth a Risk Factor for Subsequent Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder in Children with Febrile Seizure?—A Retrospective Study

by Chien-Heng Lin, Wei-De Lin, I-Ching Chou, Inn-Chi Lee and Syuan-Yu Hong

Life 2021, 11(8), 854; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080854 - 20 Aug 2021

Cited by 3 | Viewed by 2324

Abstract

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder [...] Read more.

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Therefore, this study investigated whether preterm birth is a risk factor for subsequent epilepsy, ASD, and ADHD in children with FS. We retrospectively collected data for children aged < 5 years with FS from 1 January 2005, to 31 December 2013. We divided these children into two groups—the premature birth group and the full-term group—and compared their incidence rates of epilepsy, ASD and ADHD. The data of 426 patients with history of febrile convulsion were retrospectively collected. The premature birth group (FS+/preterm+) had 108 patients and the full-term group (FS+/preterm−) had 318 patients. The overall epilepsy risk in the FS+/preterm+ group was higher than in the FS+/preterm− group (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.14–5.58; p = 0.02). The overall risk of ADHD in the FS+/preterm+ group was higher than that in the FS+/preterm− group (OR, 6.41; 95% CI, 3.39–12.09; p = 0.0001). In addition, children with FS+/preterm+ had 16.9 times (95% CI, 4.79–59.7; p = 0.0001) higher odds of having ASD compared with those with FS+/preterm−. Preterm birth may be a risk factor for subsequent epilepsy, ASD and ADHD in children with FS. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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Review

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19 pages, 9865 KiB

Open AccessEditor’s ChoiceReview

Pediatric Neuromyelitis Optica Spectrum Disorder: Case Series and Literature Review

by Michela Ada Noris Ferilli, Roberto Paparella, Ilaria Morandini, Laura Papetti, Lorenzo Figà Talamanca, Claudia Ruscitto, Fabiana Ursitti, Romina Moavero, Giorgia Sforza, Samuela Tarantino, Martina Proietti Checchi, Federico Vigevano and Massimiliano Valeriani

Life 2022, 12(1), 19; https://0-doi-org.brum.beds.ac.uk/10.3390/life12010019 - 23 Dec 2021

Cited by 5 | Viewed by 4259

Abstract

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray [...] Read more.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray matter. The aquaporin-4 antibody (AQP4-IgG) is specific for NMOSD. Recently, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been found in a group of AQP4-IgG negative patients. NMOSD is rare among children and adolescents, but early diagnosis is important to start adequate therapy. In this report, we present cases of seven pediatric patients with NMOSD and we review the clinical and neuroimaging characteristics, diagnosis, and treatment of NMOSD in children. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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31 pages, 2617 KiB

Open AccessReview

Telomeres and Cancer

by Hueng-Chuen Fan, Fung-Wei Chang, Jeng-Dau Tsai, Kao-Min Lin, Chuan-Mu Chen, Shinn-Zong Lin, Ching-Ann Liu and Horng-Jyh Harn

Life 2021, 11(12), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/life11121405 - 16 Dec 2021

Cited by 13 | Viewed by 4858

Abstract

Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the [...] Read more.

Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the RNA metabolism pathway components. As dysfunctional telomere maintenance and telomerase activation are associated with several human diseases, including cancer, the molecular mechanisms behind telomere length regulation and protection need particular emphasis. Cancer cells exhibit telomerase activation, enabling replicative immortality. Telomerase reverse transcriptase (TERT) activation is involved in cancer development through diverse activities other than mediating telomere elongation. This review describes the telomere functions, the role of functional modulators, the implications in cancer development, and the future therapeutic opportunities. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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11 pages, 942 KiB

Open AccessReview

Approach to Neurological Channelopathies and Neurometabolic Disorders in Newborns

by Inn-Chi Lee

Life 2021, 11(11), 1244; https://doi.org/10.3390/life11111244 - 16 Nov 2021

Cited by 3 | Viewed by 2759

Abstract

Ion channel disorders (channelopathies) can affect any organ system in newborns before 2 months of life, including the skeletal muscle and central nervous system. Channelopathies in newborns can manifest as seizure disorders, which is a critical issue as early onset seizures can mimic [...] Read more.

Ion channel disorders (channelopathies) can affect any organ system in newborns before 2 months of life, including the skeletal muscle and central nervous system. Channelopathies in newborns can manifest as seizure disorders, which is a critical issue as early onset seizures can mimic the presentation of neurometabolic disorders. Seizures in channelopathies can either be focal or generalized, and range in severity from benign to epileptic encephalopathies that may lead to developmental regression and eventually premature death. The presenting symptoms of channelopathies are challenging for clinicians to decipher, such that an extensive diagnostic survey through a precise step-by-step process is vital. Early diagnosis of a newborn’s disease, either as a channelopathy or neurometabolic disorder, is important for the long-term neurodevelopment of the child. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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24 pages, 3405 KiB

Open AccessReview

Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

by Hueng-Chuen Fan, Hsiu-Fen Lee, Chen-Tang Yue and Ching-Shiang Chi

Life 2021, 11(11), 1111; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111111 - 20 Oct 2021

Cited by 10 | Viewed by 6249

Abstract

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial [...] Read more.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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