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Fulltext Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

Ling KH, Hewitt CA, Tan KL, Cheah PS, Vidyadaran S, Lai MI, et al.

BMC Genomics, 2014;15:624.
PMID: 25052193 DOI: 10.1186/1471-2164-15-624

The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84.

Matched MeSH terms: Down Syndrome/genetics*
Fulltext Malocclusion and orthodontic treatment need evaluated among subjects with Down syndrome using the Dental Aesthetic Index (DAI)

Abdul Rahim FS, Mohamed AM, Nor MM, Saub R

Angle Orthod, 2014 Jul;84(4):600-6.
PMID: 24417495 DOI: 10.2319/062813-480.1

OBJECTIVE: To determine the prevalence of malocclusion and need for orthodontic treatment among persons with Down Syndrome (DS).
MATERIALS AND METHODS: Study participants were 113 persons with DS from the selected community-based rehabilitation center who fulfilled the inclusion and exclusion criteria. Ten occlusal characteristics of the Dental Aesthetic Index (DAI) were measured on study models to determine the degree of malocclusion. A single score represented the dentofacial anomalies, determined the level of severity, and determined the need for orthodontic treatment.
RESULTS: Crowding in the anterior maxillary and mandibular arch was the main malocclusion problems among the subjects with DS. Comparison between age group and genders revealed no significant differences in four categories of orthodontic treatment need (P > .05).
CONCLUSION: Most of the subjects with DS (94; 83.2%) had severe and very severe malocclusion, which indicated a desirable and mandatory need for orthodontic treatment.

Matched MeSH terms: Down Syndrome/epidemiology*
Fulltext Low levels of caries in aggressive periodontitis: A literature review

Sulugodu Ramachandra S

Saudi Dent J, 2014 Apr;26(2):47-9.
PMID: 25408595 DOI: 10.1016/j.sdentj.2013.12.002

This article is a traditional literature review on caries levels in aggressive periodontitis. Aggressive periodontitis generally affects systemically healthy individuals aged <30 years (older individuals can also be affected) and is characterized by a young age of onset, rapid rate of disease progression, and familial aggregation of cases. Dental caries is caused by the dissolution of enamel by acid-producing bacteria present in the plaque biofilm, especially when the biofilm reaches critical mass due to improper oral hygiene. The association between caries level and aggressive periodontitis has long been debated. Initial research indicated that caries levels were high in patients with aggressive periodontitis, but high-quality studies have consistently shown that caries and aggressive periodontitis are inversely related. A recent in vitro study showed that Streptococcus mutans was killed more readily in the saliva of patients with aggressive periodontitis and Aggregatibacter actinomycetemcomitans positivity than in patients with A. actinomycetemcomitans negativity. Other mechanisms possibly explaining the inverse relationship between caries and aggressive periodontitis in cases of Down's syndrome are also discussed in this literature review. The usefulness of caries level in the diagnosis of aggressive periodontitis in developing countries such as India, where the disease is diagnosed primarily on the basis of clinical and radiographic features and familial history is also discussed.

Matched MeSH terms: Down Syndrome
Fulltext CRISPR Gene-Editing Models Geared Toward Therapy for Hereditary and Developmental Neurological Disorders

Wong PK, Cheah FC, Syafruddin SE, Mohtar MA, Azmi N, Ng PY, et al.

Front Pediatr, 2021;9:592571.
PMID: 33791256 DOI: 10.3389/fped.2021.592571

Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.

Matched MeSH terms: Down Syndrome
Fulltext Karyotype pattern and maternal age distribution in down syndrome patients analyzed at Human Genome Centre, University Sains Malaysia, Kelantan

Siti Mariam I, Suhaida MA, Tarmizi AB, Norhasimah M, Nor Atifah MA, Kannan, T. P., et al.

Buletin Persatuan Genetik Malaysia, 2006;12(1):6-9.
MyJurnal

Down Syndrome (DS), is a complex genetic disease resulting from the presence of 3 copies of chromosome 21. It is the most common autosomal abnormality among live births and the most commonly recognized genetic cause of mental retardation. The only well established risk factor for DS is advanced maternal age. The Human Genome Center , University Sains Malaysia, Kelantan has been carrying out cytogenetic studies in DS patients. Here we, report the karyotype pattern of Down Syndrome patients in correlation with maternal age, among referral cases to our Center.

Matched MeSH terms: Down Syndrome
Down syndrome as a result of de novo robertsonian translocation involving chromosome 14 and 21: a case report

Norhasimah, M.M., Ahmad Tarmizi, A.B., Azman, B.A., Zilfalil, B.A., Ankathil, R.

Malaysian Journal of Paediatrics and Child Health, 2007;15(1):46-49.
MyJurnal

Generally, the karyotype profile of Down Syndrome has been reported to be full trisomy 21 in 92% of patients, mosaic trisomy 21 in 4% of patients and translocation involving chromosome 21 in 4% of patients in most of the population groups worldwide. But, karyotype analysis of 149 DS patients at the Human Genome Center, USM, during the past five years revealed that free trisomy accounted for 94.6%, mosaic trisomy 21 for 4.7% and translocation involving chromosome 21 in 0.7% of the Down Syndrome etiology in North East Malaysian population, indicating a low frequency of translocation DS in this region. Here, we report one case of translocation Down Syndrome encountered during karyotype analysis of 149 DS cases. Karyotype showed a robertsonian translocation where an entire extra chromosome 21 was attached to the centromere of one of the chromosome 14, resulting in a derivative chromosome 14 with attached chromosome 21. Karyotype analysis of the parents revealed a normal 46,XY pattern for father and 46,XX pattern for mother indicating that this robertsonian translocation had arisen de novo either prior to or at conception.

Matched MeSH terms: Down Syndrome
Fulltext Knowledge and perception regarding prenatal genetic screening of thalassemia, down syndrome and neural tube defects: a study among IIUM Kuantan undergraduates

Nur Sajidah Sulaiman, Norafiza Zainuddin

Malaysian Journal of Public Health Medicine, 2018;18(1):0-0.
MyJurnal

Prenatal genetic screening is offered during pregnancy to detect foetuses that have certain diseases. It is widely used in the detection of congenital malformation which results in foetal birth defects. Unawareness of the society on the importance of prenatal genetic testing contributes to the increase in the birth defect rate.Future parents should be exposed with the importance in performing prenatal genetic screening.The purpose of this study was to examine the knowledge and perception level of International Islamic University Malaysia (IIUM) Kuantan students regarding prenatal genetic screening thalassemia, Down syndrome and neural tube defects.This is a cross-sectional study whereby192 respondents were selected using convenience sampling method. A set of close-ended questionnaire was distributed among students in IIUM Kuantan. Independent t-test, parametric test (One- Way ANOVA test), non-parametric test (Mann-Whitney test) and correlation coefficient(Pearson) were used to find all related factors influencing knowledge and perception and to find association between knowledge and perception of IIUM Kuantan students.From this study, it was found that the level of knowledge and perception of IIUM Kuantan students regarding prenatal genetic screening of thalassemia, Down syndrome and neural tube defects was relatively high. Married students hada betterknowledge compared to unmarriedstudents (p=0.008). Moreover, students from Kulliyyah (Faculty) of Medicine had adequate level of knowledge (p

Matched MeSH terms: Down Syndrome
Fulltext Expression profiling of genes involved in the development and function of skeletal muscles in ts1cje mouse model of Down Syndrome

Pike-See Cheah, Usman Bala, King-Hwa Ling

Malaysian Journal of Medicine and Health Sciences, 2018;14(101):12-19.
MyJurnal

Introduction: Down syndrome (DS) is caused by trisomy of human chromosome 21 (HSA21). Motor dysfunction due to hypotonia has limited labour productivity and have significant effects on socio-economic status in DS individuals. Ts1Cje, a mouse model of DS that exhibits muscle weakness was employed, to investigate the expression profile of selected trisomic and disomic genes involved in skeletal muscle structure and function. Methods: Quadriceps and triceps were harvested from the Ts1Cje (C57BL/6) postnatal day 60-70 mice and corresponding wild-type littermates. Total RNA extracted from these tissues was subjected for quantitative expression profiling of three trisomic genes (Itsn1, Synj1 and Rcan1) involved in neurotransmission and six disomic genes (Lamc1, Leprel1, Myl6b, Msn, Pgm5 and Tmod1) essential for maintenance of muscle structure and function. Real-time quantitative PCR method was used for the profiling. Results: Differential gene expression in DS is reflected by 1.5-fold or more increase in the level of expression as predicted by the gene dosage imbalance hypothesis. The analysis showed no significant changes in the expression level of trisomic genes (Itsn1, Synj1 and Rcan1). On contrary, disomic genes, Leprel1 and Pgm5, were upregulated for more than 1.5-fold in DS quadriceps whereas Lamc1, Myl6b and Pgm5 were upregulated for more than 1.5 fold in DS triceps as compared to the wild-type group. Conclusions: Our findings suggest that the dysregulation of Lamc1, Leprel1, Myl6b and Pgm5 genes is associated to muscle weakness seen in Ts1Cje and may play a role in molecular pathogenesis of muscle weakness in DS.

Matched MeSH terms: Down Syndrome
Fulltext Cellular function of satellite cells does not play a role in muscle weakness of adult Ts1Cje mice

Lim, Chai Ling, Usman Bala, Leong, Melody Pui-Yee, Johnson Stanslas, Rajesh Ramasamy, Ling, King-Hwa, et al.

Neuroscience Research Notes, 2018;1(1):3-10.
MyJurnal

Down syndrome (DS) is a genetic condition resulting from triplication of human chromosome (HSA)21. Besides intellectual disability, DS is frequently associated with hypotonia. Satellite cells are the resident cells that provides robust and remarkable regenerative capacity to the skeletal muscles, and its population size has been reported to be disease-associated. However, little is known about the population size of satellite cells in DS and the association of its intrinsic cellular functionality and hypotonia seen in DS. Here, we studied the Ts1Cje mouse, a DS murine model displays the muscle weakness characteristic. Satellite cell populations were immunostained with Pax7 and myonuclei numbers in the Ts1Cje extensor digitorum longus muscle were assessed. Their cellular function was further determined via in vitro assay in high-serum conditioned medium. Subsequently, the in vitro self-renewal, proliferative, and differentiation activities of these myogenic precursor cells were assessed after 24, 48, and 72h using Pax7, MyoD, and Ki67 immunomarkers. Our results showed that the population and functionality of Ts1Cje satellite cell did not differ significantly when compared to the wildtype cells isolated from disomic littermates. In conclusion, our findings indicated that intrinsic cellular functionality of the satellite cells, do not contribute to muscle weakness in Ts1Cje mouse.

Matched MeSH terms: Down Syndrome
Postintravenous immunoglobulin stroke in a toddler with Down syndrome: a diagnostic challenge

Toh TH, Siew EC, Chieng CH, Mohd Ismail HI

BMJ Case Rep, 2020 May 18;13(5).
PMID: 32430349 DOI: 10.1136/bcr-2019-233149

Children with Down syndrome have a higher risk of stroke. Similarly, intravenous immunoglobulin (IV Ig) is also known to cause a stroke. We reported a 3-year-old boy with Down syndrome who presented with severe pneumonia and received IV Ig. He developed right hemiparesis 60 hours after the infusion. Blood investigations, echocardiography and carotid Doppler did not suggest vasculitis, thrombophilia or extracranial dissection. Brain computerised tomography (CT) showed acute left frontal and parietal infarcts. Initial magnetic resonance angiography (MRA) of cerebral vessels showed short segment attenuations of both proximal middle cerebral arteries and reduction in the calibre of bilateral supraclinoid internal carotid arteries. The boy was treated with enoxaparin and aspirin. He only had partial recovery of the hemiparesis on follow-up. A repeat MRA 13 months later showed parenchymal collateral vessels suggestive of moyamoya disease. We recommend imaging the cerebral vessels in children with a high risk of moyamoya before giving IV Ig.

Matched MeSH terms: Down Syndrome
Dexmedetomidine and ketamine sedation for dental extraction in children with cyanotic heart disease

Hasan MS, Chan L

J Oral Maxillofac Surg, 2014 Oct;72(10):1920.e1-4.
PMID: 24985961 DOI: 10.1016/j.joms.2014.03.032

Treating children with cyanotic congenital heart disease poses many challenges to anesthesiologists because of the multiple problems associated with the condition. The anesthetic technique and drugs used perioperatively can affect a patient's physiologic status during surgery. The adherence to certain hemodynamic objectives and the avoidance of factors that could worsen the abnormal cardiopulmonary physiology cannot be overemphasized. In the present case series, we describe the use of a dexmedetomidine-ketamine combination for dental extraction in spontaneously breathing children with cyanotic congenital heart disease. The anesthetic concerns regarding airway management, the pharmacologic effects of drugs, and maintenance of adequate hemodynamic, blood gases, and acid-base status are discussed.

Matched MeSH terms: Down Syndrome/complications
Fulltext Transcriptomic profiling of skeletal muscle from the Ts1Cje mouse model of Down syndrome suggests dysregulation of trisomic genes associated with neuromuscular junction signaling, oxidative stress and chronic inflammation

Leong, Melody Pui Yee, Usman Bala, Lim, Chai Ling, Rozita Rosli, Cheah, Pike-See, Ling, King-Hwa

Neuroscience Research Notes, 2018;1(1):21-41.
MyJurnal

Ts1Cje is a mouse model of Down syndrome (DS) with partial triplication of chromosome 16, which encompasses a high number of human chromosome 21 (HSA21) orthologous genes. The mouse model exhibits muscle weakness resembling hypotonia in DS individuals. The effect of extra gene dosages on muscle weakness or hypotonia in Ts1Cje and DS individuals remains unknown. To identify molecular dysregulation of the skeletal muscle, we compared the transcriptomic signatures of soleus and extensor digitorum longus (EDL) muscles between the adult Ts1Cje and disomic littermates. A total of 166 and 262 differentially expressed protein-coding genes (DEGs) were identified in the soleus and EDL muscles, respectively. The partial trisomy of MMU16 in Ts1Cje mice has a greater effect on gene expression in EDL. Top-down clustering analysis of all DEGs for represented functional ontologies revealed 5 functional clusters in soleus associated with signal transduction, development of reproductive system, nucleic acid biosynthesis, protein modification and metabolism as well as regulation of gene expression. On the other hand, only 3 functional clusters were observed for EDL namely neuron and cell development, protein modification and metabolic processes as well as ion transport. A total of 11 selected DEGs were validated using qPCR (disomic DEGs: Mansc1; trisomic DEGs: Itsn1, Rcan1, Synj1, Donson, Dyrk1a, Ifnar1, Ifnar2, Runx1, Sod1 and Tmem50b). The validated DEGs were implicated in neuromuscular junction signalling (Itsn1, Syn1), oxidative stress (Sod1, Runx1) and chronic inflammation processes (Runx1, Rcan1, Ifnar1, Ifnar2). Other validated DEGs have not been well-documented as involved in the skeletal muscle development or function, thus serve as interesting novel candidates for future investigations. To our knowledge, the study was the first attempt to determine the transcriptomic profiles of both soleus and EDL muscles in Ts1Cje mice. It provides new insights on the possible disrupted molecular pathways associated with hypotonia in DS individuals.

Matched MeSH terms: Down Syndrome

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