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Dermatoglyphics of Down's syndrome patients in Malays--a comparative study

Than M, Myat KA, Khadijah S, Jamaludin N, Isa MN

Anthropol Anz, 1998 Dec;56(4):351-65.
PMID: 10027045

There has been no recent report on the dermatoglyphics of the Malays (normal population as well as patients with Down's syndrome). A study on the frequencies of the dermal patterns (dermatoglyphics) of the digits, palms and hallucal areas was done therefore in 40 Malay patients with Down's syndrome and 200 unrelated normal controls. Only the patients with the standard 21 trisomy karyotype were included in the study. Comparison was made with the published data on studies done in various racial groups. Significant differences of the dermal patterns were found not only between the controls but also among patients of different races.

Matched MeSH terms: Down Syndrome/genetics*
Fulltext Assessment and Clinical Utility of a Non-Next-Generation Sequencing-Based Non-Invasive Prenatal Testing Technology

Gormus U, Chaubey A, Shenoy S, Wong YW, Chan LY, Choo BP, et al.

Curr Issues Mol Biol, 2021 Aug 17;43(2):958-964.
PMID: 34449543 DOI: 10.3390/cimb43020068

Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35-100.00%); 100.00% sensitivity for T18 (71.51-100.00%); and 100.00% sensitivity for T13 analyses (66.37-100.00%). The specificities were >99% for each trisomy (99.7% (99.01-99.97%) for T21; 99.5% (98.62-99.85%) for T18; 99.7% (99.03-99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.

Matched MeSH terms: Down Syndrome/genetics
Identification of chromosome 21 materials using the whole chromosome 21 specific library

Isa MN, Boyd E, Turner TL, Tolmie J, Connor JM

Southeast Asian J. Trop. Med. Public Health, 1995;26 Suppl 1:92-5.
PMID: 8629150

The chromosome in situ suppression hybridization or chromosome painting technic was applied to confirm and eliminate the markers involving chromosome 21 segments using a chromosome 21 DNA library. The library ATCCLL21SNO2 was amplified, directly biotinylated using the polymerase chain reaction. The results demonstrated a translocation of chromosome 21 material on chromosome 2 and X and eliminate the origin of the marker. Thus, the technique provides an important tool to complement the conventional G-banding technic.

Matched MeSH terms: Down Syndrome/genetics*
Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje down syndrome mouse model

Lee HC, Md Yusof HH, Leong MP, Zainal Abidin S, Seth EA, Hewitt CA, et al.

Int J Neurosci, 2019 Sep;129(9):871-881.
PMID: 30775947 DOI: 10.1080/00207454.2019.1580280

Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.

Matched MeSH terms: Down Syndrome/genetics*
Fulltext Cytogenetic and clinical profile of Down syndrome in Northeast Malaysia

Azman BZ, Ankathil R, Siti Mariam I, Suhaida MA, Norhashimah M, Tarmizi AB, et al.

Singapore Med J, 2007 Jun;48(6):550-4.
PMID: 17538755

This study was designed to evaluate the karyotype pattern, clinical features and other systemic anomalies of patients with Down syndrome in Malaysia.

Matched MeSH terms: Down Syndrome/genetics*
Fulltext GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder

Lum SH, Choong SS, Krishnan S, Mohamed Z, Ariffin H

Singapore Med J, 2016 Jun;57(6):320-4.
PMID: 27353457 DOI: 10.11622/smedj.2016106

INTRODUCTION: Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum. Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events.
METHODS: We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre.
RESULTS: Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. All identified mutations were located in exon 2 and the majority were sequence-terminating insertions or deletions (66.7%), including several hitherto unreported mutations (12 out of 15).
CONCLUSION: The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort.

Matched MeSH terms: Down Syndrome/genetics*
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*
GATA1 mutations in patients with down syndrome and acute megakaryoblastic leukaemia do not always confer a good prognosis

Ariffin H, Garcia JC, Daud SS, Ibrahim K, Aizah N, Ong GB, et al.

Pediatr Blood Cancer, 2009 Jul;53(1):108-11.
PMID: 19260099 DOI: 10.1002/pbc.21983

Children with Down syndrome and acute megakaryoblastic leukemia (DS-AMKL) have been shown to have increased sensitivity to cytarabine based chemotherapy. The excellent prognosis in patients with DS-AMKL may be due to mutations in the GATA1 gene leading to reduced expression of the enzyme cytidine deaminase. This leads to a decreased ability to convert cytarabine into its inactive metabolite, resulting in high intracellular concentration of this cytotoxic agent. We report two cases of DS-AMKL with GATA1 mutations who had poor outcome. These patients had high expression levels of cytidine deaminase mRNA transcripts. We speculate that other factors can affect overall outcome in patients with DS-AMKL irrespective of the presence of GATA1 mutations.

Matched MeSH terms: Down Syndrome/genetics*
Down syndrome in diverse populations

Kruszka P, Porras AR, Sobering AK, Ikolo FA, La Qua S, Shotelersuk V, et al.

Am J Med Genet A, 2017 Jan;173(1):42-53.
PMID: 27991738 DOI: 10.1002/ajmg.a.38043

Down syndrome is the most common cause of cognitive impairment and presents clinically with universally recognizable signs and symptoms. In this study, we focus on exam findings and digital facial analysis technology in individuals with Down syndrome in diverse populations. Photos and clinical information were collected on 65 individuals from 13 countries, 56.9% were male and the average age was 6.6 years (range 1 month to 26 years; SD = 6.6 years). Subjective findings showed that clinical features were different across ethnicities (Africans, Asians, and Latin Americans), including brachycephaly, ear anomalies, clinodactyly, sandal gap, and abundant neck skin, which were all significantly less frequent in Africans (P Down syndrome with a sensitivity of 0.961, specificity of 0.924, and accuracy of 0.943. Only the angles at medial canthus and ala of the nose were common significant findings amongst different ethnicities (Caucasians, Africans, and Asians) when compared to ethnically matched controls. The Asian group had the least number of significant digital facial biometrics at 4, compared to Caucasians at 8 and Africans at 7. In conclusion, this study displays the wide variety of findings across different geographic populations in Down syndrome and demonstrates the accuracy and promise of digital facial analysis technology in the diagnosis of Down syndrome internationally. © 2016 Wiley Periodicals, Inc.

Matched MeSH terms: Down Syndrome/genetics
Cytogenetic profile of patients with clinical spectrum of ambiguous genitalia, amenorrhea, and Turner phenotype: A 21-year single-center experience

Elkarhat Z, Belkady B, Charoute H, Zarouf L, Razoki L, Aboulfaraj J, et al.

Am J Med Genet A, 2019 08;179(8):1516-1524.
PMID: 31207162 DOI: 10.1002/ajmg.a.61257

The aim of the present study was to determine the frequency and nature of chromosomal abnormalities involved in patients with the clinical spectrum of ambiguous genitalia (AG), amenorrhea, and Turner phenotype, in order to compare them with those reported elsewhere. The study was conducted in the Cytogenetic Department of Pasteur Institute of Morocco, and it reports on the patients who were recruited between 1996 and 2016. Cytogenetic analysis was performed according to the standard method. Among 1,415 patients, chromosomal abnormalities were identified in 7.13% (48/673) of patients with AG, 17.39% (28/161) of patients with primary amenorrhea (PA), 4% (1/25) of patients with secondary amenorrhea, and 23.20% (129/556) of patients with Turner phenotype. However, Turner syndrome was diagnosed in 0.89% (6/673) of patients with AG, 10.56% (17/161) of patients with PA, and 19.78% (110/556) of patients with Turner phenotype. In addition, Klinefelter syndrome and mixed gonadal dysgenesis were confirmed in 2.97% and 1.93% of patients, respectively, with AG, while, chimerism, trisomy 8, and trisomy 13 were confirmed only in 0.15% each. Trisomy 21 was confirmed in patients with AG and Turner phenotype (0.15% and 0.36%, respectively). Moreover, 5.60% (9/161) of patients with PA have been diagnosed as having sex reversal. Thus, the frequency of chromosomal abnormalities observed in Moroccan patients with PA is comparable to that reported in Tunisia, Turkey, Iran, and Hong Kong. However, the frequency is significantly less than that identified in India, Malaysia, Italy, and Romania.

Matched MeSH terms: Down Syndrome/genetics
The Potential Role of miRNAs as Predictive Biomarkers in Neurodevelopmental Disorders

Juvale IIA, Che Has AT

J Mol Neurosci, 2021 Jul;71(7):1338-1355.
PMID: 33774758 DOI: 10.1007/s12031-021-01825-7

Neurodevelopmental disorders are defined as a set of abnormal brain developmental conditions marked by the early childhood onset of cognitive, behavioral, and functional deficits leading to memory and learning problems, emotional instability, and impulsivity. Autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, fragile X syndrome, and Down's syndrome are a few known examples of neurodevelopmental disorders. Although they are relatively common in both developed and developing countries, very little is currently known about their underlying molecular mechanisms. Both genetic and environmental factors are known to increase the risk of neurodevelopmental disorders. Current diagnostic and screening tests for neurodevelopmental disorders are not reliable; hence, individuals with neurodevelopmental disorders are often diagnosed in the later stages. This negatively affects their prognosis and quality of life, prompting the need for a better diagnostic biomarker. Recent studies on microRNAs and their altered regulation in diseases have shed some light on the possible role they could play in the development of the central nervous system. This review attempts to elucidate our current understanding of the role that microRNAs play in neurodevelopmental disorders with the hope of utilizing them as potential biomarkers in the future.

Matched MeSH terms: Down Syndrome/genetics