Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21

Latar Belakang: Sindrom Down merupakan kelainan kromosom autosomal yang terjadi akibat trisomi seluruh atau sebagian dari kromosom 21, yang terjadi kurang lebih 1 dari 700 kelahiran hidup. Berbagai studi mendapatkan bahwa gangguan makan (feeding difficulty) dan disfagia merupakan masalah yang umum terjadi dan terkadang persisten pada anak sindrom Down. Tujuan: Memaparkan karakteristik kelainan disfagia fase oral dan fase faring yang dapat timbul pada anak dengan sindrom Down menggunakan instrument pemeriksaan Fiberoptic Endoscopic Evaluation of Swallowing (FEES). Laporan kasus: Dilaporkan 8 pasien anak dengan sindrom Down yang didapatkan dari rekam medis pasien sejak Oktober 2016 hingga September 2017, yang dilakukan pemeriksaan FEES di Poli Endoskopi Bronkoesofagologi Departemen Telinga Hidung Tenggorok-Bedah Kepala Leher (THT-KL) Rumah Sakit Dr. Cipto Mangunkusumo. Metode: Pencarian literatur secara terstruktur dilakukan dengan menggunakan Pubmed, ClinicalKey, Cochrane, dan Google scholar, sesuai dengan pertanyaan klinis berupa bagaimana karakteristik disfagia pada pasien anak dengan sindrom Down melalui pemeriksaan FEES. Pemilihan artikel dilakukan berdasarkan kriteria inklusi dan eksklusi. Hasil didapatkan 1 artikel yang relevan. Hasil: Artikel yang didapat merupakan suatu studi retrospektif yang melaporkan gambaran deskriptif karakteristik disfagia pada anak dengan sindrom Down. Kesimpulan: Kelainan anatomis pada sindrom Down berperan pada terjadinya gangguan makan dan disfagia. ABSTRACTBackground: Down syndrome is an autosomal chromosomal disorder caused by entire or partial trisomy of chromosome 21, which occurs in approximately 1 out of 700 live births. Several studies had found that feeding difficulty and swallowing disorder (dysphagia) are common and persistent problems in children with Down syndrome. Purpose: to describe characteristics of abnormalities that can occur in children with Down syndrome using the Fiberoptic Endoscopic Evaluation of Swallowing (FEES) examination. Case report: 8 Pediatric patients with Down syndrome, obtained from medical record of FEES examination in Endoscopic Bronchoesophagology Clinic of Otorhinolaryngology-Head and Neck Surgery Department (ENT-HNS) Cipto Mangunkusumo Hospital, from October 2016 up to September 2017. Method: A structured literature search was performed using Pubmed, ClinicalKey, Cochrane, and Google scholar, according to clinical question of how the characteristics of dysphagia in pediatric patients with Down syndrome through FEES examination? The selection of articles is based on inclusion and exclusion criteria which resulted in 1 relevant paper. Results: The article obtained was a retrospective study reporting descriptive characteristics of dysphagia in children with Down syndrome. Conclusion: Anatomical abnormalities in children with Down syndrome play a role in eating disorders and dysphagia. Keywords:

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Partial trisomy and tetrasomy of chromosome 21 without Down Syndrome phenotype and short overview of genotype-phenotype correlation. A case report

Biomedical Papers ◽

10.5507/bp.2013.077 ◽

2014 ◽

Vol 158 (2) ◽

pp. 321-325 ◽

Cited By ~ 14

Author(s):

Pavlina Capkova ◽

Nadezda Misovicova ◽

Dita Vrbicka

Keyword(s):

Down Syndrome ◽

Case Report ◽

Partial Trisomy ◽

Chromosome 21 ◽

Phenotype Correlation ◽

Short Overview ◽

Genotype Phenotype Correlation ◽

Down Syndrome Phenotype

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Down syndrome with partial trisomy of chromosome 21 because of a de-novo unbalanced translocation t(13;21)(q10;q22)

Clinical Dysmorphology ◽

10.1097/mcd.0b013e32835909cc ◽

2012 ◽

Vol 21 (4) ◽

pp. 200-203 ◽

Cited By ~ 1

Author(s):

Emilie Maciejewski ◽

Jacqueline Vigneron ◽

Laetitia Lambert ◽

Céline Bonnet ◽

Jean-Michel Hascoët

Keyword(s):

Down Syndrome ◽

De Novo ◽

Partial Trisomy ◽

Chromosome 21 ◽

Unbalanced Translocation

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What people with Down Syndrome can teach us about cardiopulmonary disease

European Respiratory Review ◽

10.1183/16000617.0098-2016 ◽

2017 ◽

Vol 26 (143) ◽

pp. 160098 ◽

Cited By ~ 16

Author(s):

Kelley L. Colvin ◽

Michael E. Yeager

Keyword(s):

Down Syndrome ◽

Partial Trisomy ◽

Chromosome 21 ◽

Health Issues ◽

Cardiopulmonary Disease ◽

Life Issues ◽

Life Threatening ◽

Immune Challenges ◽

Tract Infections

Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations (particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.

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Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.38497 ◽

2017 ◽

Vol 173 (12) ◽

pp. 3153-3157

Author(s):

Manesha Putra ◽

Urvashi Surti ◽

Jie Hu ◽

Deana Steele ◽

Michele Clemens ◽

...

Keyword(s):

Down Syndrome ◽

Chromosome 21 ◽

Partial Monosomy ◽

Down Syndrome Phenotype ◽

Isodicentric Chromosome

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Hematopoietic defects in the Ts1Cje mouse model of Down syndrome

Blood ◽

10.1182/blood-2008-06-161422 ◽

2009 ◽

Vol 113 (9) ◽

pp. 1929-1937 ◽

Cited By ~ 36

Author(s):

Catherine L. Carmichael ◽

Ian J. Majewski ◽

Warren S. Alexander ◽

Donald Metcalf ◽

Douglas J. Hilton ◽

...

Keyword(s):

Down Syndrome ◽

Mouse Model ◽

Cell Function ◽

Fetal Liver ◽

Partial Trisomy ◽

Chromosome 21 ◽

Loss Of Function ◽

Premalignant Disease ◽

Acute Megakaryocytic Leukemia ◽

Insight Into

Down syndrome (DS) persons are born with various hematopoietic abnormalities, ranging from relatively benign, such as neutrophilia and macrocytosis, to a more severe transient myeloproliferative disorder (TMD). In most cases, these abnormalities resolve in the first few months to years of life. However, sometimes the TMD represents a premalignant disease that develops into acute megakaryocytic leukemia (AMKL), usually in association with acquired GATA1 mutations. To gain insight into the mechanisms responsible for these abnormalities, we analyzed the hematopoietic development of the Ts1Cje mouse model of DS. Our analyses identified defects in mature blood cells, including macrocytosis and anemia, as well as abnormalities in fetal liver and bone marrow stem and progenitor cell function. Despite these defects, the Ts1Cje mice do not develop disease resembling either TMD or AMKL, and this was not altered by a loss of function allele of Gata1. Thus, loss of Gata1 and partial trisomy of chromosome 21 orthologs, when combined, do not appear to be sufficient to induce TMD or AMKL-like phenotypes in mice.

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Structural Characterization of the Highly Restricted Down Syndrome Critical Region on 21q22.13: New KCNJ6 and DSCR4 Transcript Isoforms

Frontiers in Genetics ◽

10.3389/fgene.2021.770359 ◽

2021 ◽

Vol 12 ◽

Author(s):

Francesca Antonaros ◽

Margherita Pitocco ◽

Domenico Abete ◽

Beatrice Vione ◽

Allison Piovesan ◽

...

Keyword(s):

Down Syndrome ◽

Intergenic Region ◽

Critical Region ◽

Partial Trisomy ◽

Cardiac Cells ◽

Chromosome 21 ◽

Ensembl Database ◽

Physiological Processes

Down syndrome (DS) is caused by trisomy of chromosome 21 and it is the most common genetic cause of intellectual disability (ID) in humans. Subjects with DS show a typical phenotype marked by facial dysmorphisms and ID. Partial trisomy 21 (PT21) is a rare genotype characterized by the duplication of a delimited chromosome 21 (Hsa21) portion and it may or may not be associated with DS diagnosis. The highly restricted Down syndrome critical region (HR-DSCR) is a region of Hsa21 present in three copies in all individuals with PT21 and a diagnosis of DS. This region, located on distal 21q22.13, is 34 kbp long and does not include characterized genes. The HR-DSCR is annotated as an intergenic region between KCNJ6-201 transcript encoding for potassium inwardly rectifying channel subfamily J member 6 and DSCR4-201 transcript encoding Down syndrome critical region 4. Two transcripts recently identified by massive RNA-sequencing (RNA-Seq) and automatically annotated on Ensembl database reveal that the HR-DSCR seems to be partially crossed by KCNJ6-202 and DSCR4-202 isoforms. KCNJ6-202 shares the coding sequence with KCNJ6-201 which is involved in many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells. DSCR4-202 transcript has the first two exons in common with DSCR4-201, the only experimentally verified gene uniquely present in Hominidae. In this study, we performed in silico and in vitro analyses of the HR-DSCR. Bioinformatic data, obtained using Sequence Read Archive (SRA) and SRA-BLAST software, were confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Sanger sequencing on a panel of human tissues. Our data demonstrate that the HR-DSCR cannot be defined as an intergenic region. Further studies are needed to investigate the functional role of the new transcripts, likely involved in DS phenotypes.

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