A Novel 4q32.3 Deletion in a Boy: Additional Signs and the Role of MARCH1

2021 ◽  
Author(s):  
Xena Giada Pappalardo ◽  
Martino Ruggieri ◽  
Raffaele Falsaperla ◽  
Salvatore Savasta ◽  
Umberto Raucci ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Growth Failure ◽  
Deletion Syndrome ◽  
Comparative Genomic ◽  
Mild Developmental Delay ◽  
Uncommon Condition ◽  
Craniofacial Features ◽  
Adducted Thumbs ◽  
Genomic Variant

AbstractThe 4q deletion syndrome is an uncommon condition manifesting with broad clinical expression and phenotypic variability. We report a 5-year-old boy affected by 4q deletion syndrome who showed minor craniofacial features, growth failure, mild developmental delay, severe speech delay, and marked irascibility and aggressivity. Moreover, he showed precocious and crowded primary dentition, digital hyperlaxity, and congenital bilateral adducted thumbs, signs which were previously unreported in the syndrome. The array comparative genomic hybridization analysis revealed a 4q partial terminal deletion of ∼329.6 kb extending from 164.703.186 to 165.032.803 nt, which includes part of MARCH1 (membrane associated ring-CH-type finger 1) gene (OMIM#613331). Same rearrangement was found in his healthy mother. Clinical phenotype of the child and its relationship to the deleted region is presented with a revision of the cases having the same copy number losses from the literature and genomic variant databases.

scholarly journals The 22q11 low copy repeats are characterized by unprecedented size and structure variability

2018 ◽  
Author(s):  
Wolfram Demaerel ◽  
Yulia Mostovoy ◽  
Feyza Yilmaz ◽  
Lisanne Vervoort ◽  
Steven Pastor ◽  
...  
Keyword(s):  
De Novo ◽  
Phenotypic Variability ◽  
Chromosomal Rearrangements ◽  
Deletion Syndrome ◽  
Genomic Disorder ◽  
Genome Variability ◽  
Low Copy Repeats ◽  
Different Populations ◽  
High Level

Abstract:Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The chromosome 22 LCRs (LCR22s) are amongst the most complex regions in the genome and their structure remains unresolved. These LCR22s mediate non-allelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS), causing the most frequent genomic disorder. Using fiber FISH optical mapping, we have de novo assembled the LCR22s in 33 cell lines. We observed a high level of variation in LCR22 structures, including 26 different haplotypes of LCR22A with alleles ranging from 250 Kb to over 2,000 Kb. An additional four haplotypes were detected using Bionano mapping. Further, Bionano maps generated from 154 individuals from different populations suggested significantly different LCR22 haplotype frequencies between populations. Furthermore, haplotype analysis in nine 22q11DS patients resulted in the localization of the NAHR site to a 160 Kb paralog between LCR22A and –D in seven patients and to a 31 Kb region in two individuals with a rearrangement between LCR22A and –B.. This 31 Kb region contains a palindromic AT-rich repeat known to be a driver of chromosomal rearrangements. Our study highlights an unprecedented level of polymorphism in the structure of LCR22s, which are likely still evolving. We present the most comprehensive map of LCR22 variation to date, paving the way towards investigating the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability in 22q11DS patients as well as in the general population.

scholarly journals Refining the Phenotype of Recurrent Rearrangements of Chromosome 16

2019 ◽  
Vol 20 (5) ◽  
pp. 1095 ◽  
Author(s):  
Serena Redaelli ◽  
Silvia Maitz ◽  
Francesca Crosti ◽  
Elena Sala ◽  
Nicoletta Villa ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Segmental Duplications ◽  
Apraxia Of Speech ◽  
Chromosome 16 ◽  
Childhood Apraxia Of Speech ◽  
Elevated Frequency

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.

scholarly journals The role of lumbar puncture in the diagnosis of subarachnoid hemorrhage when computed tomography is unavailable

CJEM ◽  
2002 ◽  
Vol 4 (02) ◽  
pp. 102-105 ◽  
Author(s):  
David Mann
Keyword(s):  
Computed Tomography ◽  
Differential Diagnosis ◽  
Subarachnoid Hemorrhage ◽  
Ct Scan ◽  
Lumbar Puncture ◽  
Uncommon Condition ◽  
Noncontrast Computed Tomography ◽  
Acute Headache ◽  
Interpretation Of Results

ABSTRACTSubarachnoid hemorrhage (SAH) is an important but uncommon condition in the differential diagnosis of acute headache. Most authorities recommend that patients with suspected SAH undergo noncontrast computed tomography (CT) as a first diagnostic intervention. If the results of the CT scan are negative, a lumbar puncture should be performed. Many nonurban Canadian hospitals do not have CT scanners and must either transfer patients or consider performing lumbar puncture prior to CT. In selected patients, performing lumbar puncture first may be an option, but timing of the procedure and the interpretation of results is important.

scholarly journals Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Pricila da Silva Cunha ◽  
Heloisa B. Pena ◽  
Carla Sustek D’Angelo ◽  
Celia P. Koiffmann ◽  
Jill A. Rosenfeld ◽  
...  
Keyword(s):  
Real Time ◽  
Diagnostic Test ◽  
Quantitative Pcr ◽  
Target Genes ◽  
Cost Effective ◽  
Qpcr Assay ◽  
Deletion Syndrome ◽  
Comparative Genomic ◽  
Real Time Quantitative Pcr ◽  
Subtelomeric Deletion

Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH), which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR) assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36:PRKCZandSKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescentin situhybridization (FISH), and/or multiplex ligation-dependent probe amplification (MLPA) all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR ofPRKCZandSKIis a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs.

A novel 5q11.2 deletion detected by microarray comparative genomic hybridisation in a child referred as a case of suspected 22q11 deletion syndrome

2004 ◽  
Vol 116 (1-2) ◽  
pp. 83-90 ◽  
Author(s):  
Katrina Prescott ◽  
Kathryn Woodfine ◽  
Paula Stubbs ◽  
Maurice Super ◽  
Bronwyn Kerr ◽  
...  
Keyword(s):  
Deletion Syndrome ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
22Q11 Deletion ◽  
22Q11 Deletion Syndrome

The Neuropathology of 1p36 Deletion Syndrome: An Autopsy Case Series

2021 ◽  
Author(s):  
Kyle S Conway ◽  
Fozia Ghafoor ◽  
Amy C Gottschalk ◽  
Joseph Laakman ◽  
Renee L Eigsti ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Single Case ◽  
Case Reports ◽  
Case Series ◽  
Deletion Syndrome ◽  
Cerebellar Hypoplasia ◽  
Autopsy Case ◽  
Single Case Report ◽  
Renal Abnormalities

Abstract 1p36 deletion syndrome is the most common terminal deletion syndrome, manifesting clinically as abnormal facies and developmental delay with frequent cardiac, skeletal, urogenital, and renal abnormalities. Limited autopsy case reports describe the neuropathology of 1p36 deletion syndrome. The most extensive single case report described a spectrum of abnormalities, mostly related to abnormal neuronal migration. We report the largest published series of 1p36 autopsy cases, with an emphasis on neuropathologic findings. Our series consists of 3 patients: 2 infants (5-hours old and 23-days old) and 1 older child (11 years). Our patients showed abnormal cortical gyration together with a spectrum of neuronal migration abnormalities, including heterotopias and hippocampal abnormalities, as well as cerebellar hypoplasia. Our findings thus support the role of neuronal migration defects in the pathogenesis of cognitive defects in 1p36 deletion syndrome and broaden the reported neuropathologic spectrum of this common syndrome.

Structural diseases of the heart: syndromes affecting the cardiovascular system

ESC CardioMed ◽  
2018 ◽  
pp. 719-722
Author(s):  
Sabine Klaassen
Keyword(s):  
Single Gene ◽  
Significant Proportion ◽  
Signal Transduction Pathway ◽  
Alagille Syndrome ◽  
Mitogen Activated Protein Kinase ◽  
Neurological Deficits ◽  
Deletion Syndrome ◽  
Gene Encoding ◽  
Mitogen Activated Protein ◽  
Craniofacial Features

Congenital heart disease (CHD) occurs in association with extracardiac anomalies or as part of an identified syndrome in 25–40% of cases. Approximately 30% of children with a chromosomal abnormality have CHD. Aneuploidy, or abnormal chromosomal number, accounts for a significant proportion of CHD. Of individuals born with trisomy 21, 50% have CHD, the most common being an atrioventricular septal defect (45%). In segmental aneuploidies, the so-called microdeletion syndromes, small submicroscopic chromosomal deletions can lead to CHD. The 22q11 deletion syndrome causes CHD with thymic and parathyroid hypoplasia (DiGeorge syndrome) and characteristic dysmorphic craniofacial features due to abnormal pharyngeal arch development. Williams–Beuren syndrome with renovascular anomalies, typical elfin facies, and neurological deficits, is characterized by cardiac involvement in the form of supravalvar aortic and peripheral pulmonic stenosis. Chromosome 1p36 deletion syndrome is the most common subterminal deletion syndrome. A substantial proportion of individuals with 1p36 deletion syndrome have CHD which may occur in the presence or absence of cardiomyopathy, most commonly left ventricular non-compaction cardiomyopathy. Single gene mutations may also cause syndromic CHD. Noonan syndrome and related disorders (‘RASopathies’) are caused by dominant gain-of-function mutations in one of the genes which encode proteins that function in the Ras/mitogen-activated protein kinase (RAS-MAPK) signal transduction pathway. Holt–Oram syndrome is associated with mutations in the transcription factor TBX5. Alagille syndrome is caused by mutations in JAG1, a gene encoding a ligand in the Notch signaling pathway. Heterotaxy syndrome, which means randomization of cardiac, pulmonary, or gastrointestinal situs, is frequently associated with CHD.

scholarly journals Growth and body composition in children with chronic kidney disease

2007 ◽  
Vol 97 (2) ◽  
pp. 232-238 ◽  
Author(s):  
R. Rashid ◽  
E. Neill ◽  
H. Maxwell ◽  
S. F. Ahmed
Keyword(s):  
Chronic Kidney Disease ◽  
Body Composition ◽  
Kidney Disease ◽  
Growth Failure ◽  
Potential Effect ◽  
Complex Problem ◽  
Physiological Mechanisms ◽  
Growth And Nutrition

Growth failure is a common yet complex problem of childhood chronic kidney disease caused by multiple factors encountered due to the primary disease or secondary to the renal impairment. This review seeks to describe the various patho-physiological mechanisms contributing to growth failure in the various stages of childhood with particular emphasis on nutritional problems and endocrine dysfunction encountered whilst managing these children. In addition, we shall examine the role of body composition in chronic kidney disease, their relationship with growth and nutrition and the potential effect of abnormalities in fat mass and lean mass on long-term morbidity and mortality.

Chronic obstructive pulmonary disease

2017 ◽  
Author(s):  
Amina Jaffer ◽  
Anant Patel ◽  
John Hurst
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Phenotypic Variability ◽  
Evidence Base ◽  
Future Research ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Potential Benefits ◽  
Learning Points

This chapter discusses the case of a 70-year-old man with his first presentation of chronic obstructive pulmonary disease. This case is used as a basis to explore and describe the diagnosis, investigation, and management of this condition. The chapter includes the evidence base and relative guidelines that support current practice, as well as highlighting useful learning points and providing expert opinion. The role of lung volume reduction surgery is discussed, and its potential benefits in selected patients highlighted. Phenotypic variability within chronic obstructive pulmonary disease is increasingly recognized, and this is discussed, including the implications on current management and future research.

Sign in / Sign up

Export Citation Format

Share Document