Partial 5p Deletion and Partial 5q Duplication in a Patient with Multiple Congenital Anomalies: A Two-Step Mechanism in Chromosomal Rearrangement Mediated by Non-Allelic Homologous Recombination

2018 ◽  
Vol 156 (2) ◽  
pp. 65-70
Author(s):  
Zhishuo Z. Ou ◽  
Sally Kochmar ◽  
Svetlana A. Yatsenko ◽  
Audrey C. Woerner ◽  
Roxanne Acquaro ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
De Novo ◽  
Chromosome Analysis ◽  
Bioinformatic Analysis ◽  
Deletion Syndrome ◽  
Fish Analysis ◽  
Feeding Difficulties ◽  
Low Copy Repeats ◽  
5P Deletion ◽  
Nonallelic Homologous Recombination

We describe a 5-month-old female who presented with clinical features of 5p deletion syndrome, including high-pitched cry, microcephaly, micrognathia, bilateral preauricular tags, bifid uvula, abnormal palmar creases, bilateral hypoplastic nipples, feeding difficulties, and developmental delay. In addition, the patient also had a cardiac defect, proximal esophageal atresia, and distal tracheoesophageal fistula. aCGH of the patient revealed a 22.9-Mb deletion of chromosome 5p15.33p14.3 and an 8.28-Mb duplication of chromosome 5q12.1q13.2. Parental chromosome analysis indicated that these alterations are de novo. Chromosome and FISH analysis demonstrated that the 5q12.1q13.2 duplicated segment was attached to the 5p14.3 region with the band 5q12.1 more distal to the centromere than the band 5q13.2. Based on the bioinformatic analysis, we postulate a mechanism for the formation of this complex rearrangement of chromosome 5 by 2-step-wise events mediate by nonallelic homologous recombination between low copy repeats. To the best of our knowledge this rearrangement found in our patient has not been reported in the literature. This report demonstrates the value of chromosome analysis in conjunction with FISH and aCGH for identification of complex rearrangements which cannot be revealed by array analysis alone.

scholarly journals A Case of 17q21.31 Microduplication and 7q31.33 Microdeletion, Associated with Developmental Delay, Microcephaly, and Mild Dysmorphic Features

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Adrian Mc Cormack ◽  
Juliet Taylor ◽  
Leah Te Weehi ◽  
Donald R. Love ◽  
Alice M. George
Keyword(s):  
Homologous Recombination ◽  
Developmental Delay ◽  
Microarray Analysis ◽  
Lower Incidence ◽  
Clinical Phenotype ◽  
Microarray Technology ◽  
Dysmorphic Features ◽  
Low Copy Repeats ◽  
Nonallelic Homologous Recombination ◽  
Chromosome Regions

Concurrent cryptic microdeletion and microduplication syndromes have recently started to reveal themselves with the advent of microarray technology. Analysis has shown that low-copy repeats (LCRs) have allowed chromosome regions throughout the genome to become hotspots for nonallelic homologous recombination to take place. Here, we report a case of a 7.5-year-old girl who manifests microcephaly, developmental delay, and mild dysmorphic features. Microarray analysis identified a microduplication in chromosome 17q21.31, which encompasses theCRHR1, MAPT,andKANSL1genes, as well as a microdeletion in chromosome 7q31.33 that is localised within theGRM8gene. To our knowledge this is one of only a few cases of 17q21.31 microduplication. The clinical phenotype of patients with this microduplication is milder than of those carrying the reciprocal microdeletions, and suggests that the lower incidence of the former compared to the latter may be due to underascertainment.

scholarly journals 22q11.2 Low Copy Repeats Expanded in the Human Lineage

2021 ◽  
Vol 12 ◽  
Author(s):  
Lisanne Vervoort ◽  
Nicolas Dierckxsens ◽  
Zjef Pereboom ◽  
Oronzo Capozzi ◽  
Mariano Rocchi ◽  
...  
Keyword(s):  
Human Population ◽  
De Novo ◽  
Phenotypic Variability ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Species Variation ◽  
Human Lineage ◽  
22Q11.2 Deletion ◽  
Functional Studies ◽  
Low Copy Repeats

Segmental duplications or low copy repeats (LCRs) constitute duplicated regions interspersed in the human genome, currently neglected in standard analyses due to their extreme complexity. Recent functional studies have indicated the potential of genes within LCRs in synaptogenesis, neuronal migration, and neocortical expansion in the human lineage. One of the regions with the highest proportion of duplicated sequence is the 22q11.2 locus, carrying eight LCRs (LCR22-A until LCR22-H), and rearrangements between them cause the 22q11.2 deletion syndrome. The LCR22-A block was recently reported to be hypervariable in the human population. It remains unknown whether this variability also exists in non-human primates, since research is strongly hampered by the presence of sequence gaps in the human and non-human primate reference genomes. To chart the LCR22 haplotypes and the associated inter- and intra-species variability, we de novo assembled the region in non-human primates by a combination of optical mapping techniques. A minimal and likely ancient haplotype is present in the chimpanzee, bonobo, and rhesus monkey without intra-species variation. In addition, the optical maps identified assembly errors and closed gaps in the orthologous chromosome 22 reference sequences. These findings indicate the LCR22 expansion to be unique to the human population, which might indicate involvement of the region in human evolution and adaptation. Those maps will enable LCR22-specific functional studies and investigate potential associations with the phenotypic variability in the 22q11.2 deletion syndrome.

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 A novel third type of recurrent NF1 microdeletion mediated by nonallelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2

2010 ◽  
Vol 31 (6) ◽  
pp. 742-751 ◽  
Author(s):  
Kathrin Bengesser ◽  
David N. Cooper ◽  
Katharina Steinmann ◽  
Lan Kluwe ◽  
Nadia A. Chuzhanova ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Low Copy Repeats ◽  
Nonallelic Homologous Recombination

Stridor as one of the symptoms of 5p deletion syndrome in a five-month-old child

2017 ◽  
Vol 6 (3) ◽  
pp. 37-42
Author(s):  
Katarzyna Malicka ◽  
Ewa Grochowska-Bohatyrewicz ◽  
Aleksandra Pietrzyk ◽  
Stecewicz Iwona ◽  
Ewa Jaworowska ◽  
...  
Keyword(s):  
Behavioral Problems ◽  
Genetic Disorder ◽  
Later Life ◽  
Deletion Syndrome ◽  
Type I ◽  
Speech Impairment ◽  
Motor Delay ◽  
Feeding Difficulties ◽  
Dysmorphic Features ◽  
5P Deletion

The 5p deletion syndrome (5p-, Cri-du-chat syndrome, CdCS) is a genetic disorder which results from a partial deletion of the short arm of chromosome 5. It was first described by Lejeune et al. in 1963. The incidence ranges from 1:15 000 to 1:50 000 live births. The 5p- is usually diagnosed in the first days of life because of the characteristic monotonous high pitched cat-like cry and relatively constant dysmorphic features. Other symptoms often present in the neonatal period include low birth weight, muscle hypotonia, asphyxia and feeding difficulties due to impaired suction and swallowing, which may all lead to failure to thrive. Organ malformations, with various larynx abnormalities, although not very frequent, can also be present. Symptoms that are prevalent in later life include severe motor delay and intellectual disability with significant speech impairment, as well as behavioral problems. The case report presents a female infant in her 5th month of life in whom, despite the typical symptoms of 5p-, stridor and episodes of choking were the main problems. Laryngotracheal endoscopy revealed the type I laryngeal cleft. Genetic analysis confirmed the diagnose of 5p- syndrome. The presented case shows that it is critically important to perform a further investigation and refer a child with laryngological problems coexisting with dysmorphic features to a clinical geneticist.

Stridor as one of the symptoms of 5p deletion syndrome in a five-month-old child

2017 ◽  
Vol 6 (3) ◽  
pp. 16-21
Author(s):  
Przemysław Hubert Krawczyk ◽  
Dariusz Kaczmarczyk
Keyword(s):  
Behavioral Problems ◽  
Genetic Disorder ◽  
Later Life ◽  
Deletion Syndrome ◽  
Type I ◽  
Speech Impairment ◽  
Motor Delay ◽  
Feeding Difficulties ◽  
Dysmorphic Features ◽  
5P Deletion

The 5p deletion syndrome (5p-, Cri-du-chat syndrome, CdCS) is a genetic disorder which results from a partial deletion of the short arm of chromosome 5. It was first described by Lejeune et al. in 1963. The incidence ranges from 1:15 000 to 1:50 000 live births. The 5p- is usually diagnosed in the first days of life because of the characteristic monotonous high pitched cat-like cry and relatively constant dysmorphic features. Other symptoms often present in the neonatal period include low birth weight, muscle hypotonia, asphyxia and feeding difficulties due to impaired suction and swallowing, which may all lead to failure to thrive. Organ malformations, with various larynx abnormalities, although not very frequent, can also be present. Symptoms that are prevalent in later life include severe motor delay and intellectual disability with significant speech impairment, as well as behavioral problems. The case report presents a female infant in her 5th month of life in whom, despite the typical symptoms of 5p-, stridor and episodes of choking were the main problems. Laryngotracheal endoscopy revealed the type I laryngeal cleft. Genetic analysis confirmed the diagnose of 5p- syndrome. The presented case shows that it is critically important to perform a further investigation and refer a child with laryngological problems coexisting with dysmorphic features to a clinical geneticist.

scholarly journals A Homozygous Deletion of the DPY19L2 Gene is a Cause of Globozoospermia in Men From the Republic of Macedonia

2013 ◽  
Vol 16 (1) ◽  
pp. 73-76 ◽  
Author(s):  
P Noveski ◽  
S Madjunkova ◽  
I Maleva ◽  
V Sotiroska ◽  
Z Petanovski ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Intracytoplasmic Sperm Injection ◽  
Case Reports ◽  
Homozygous Deletion ◽  
Success Rates ◽  
Republic Of Macedonia ◽  
Low Copy Repeats ◽  
Geographic Regions ◽  
The Republic ◽  
Nonallelic Homologous Recombination

Abstract Globozoospermia is a rare but severe teratozoospermia, characterized by ejaculates consisting completely of round-headed spermatozoa that lack an acrosome or, in partial globozoospermia, containing a variable proportion (20.0-90.0%) of acrosomeless spermatozoa. Men that are affected with total globozoospermia are infertile, and even the application of intracytoplasmic sperm injection (ICSI) has met with disappointingly low success rates. In humans, several case reports of globozoospermia have demonstrated that two or more siblings were affected in each family, which suggested a genetic component to this disease. Currently, three genes are known to be associated with total globozoospermia in humans, SPATA16, PICK1 and DPY19L2 genes. Mutations in SPATA16 and PICK1 are rare causes of globozoospermia, found in only one patient each. Several studies have suggested that DPY19L2 mutations are the major cause of globozoospermia in patients from different ethnic origins and different geographic regions. The most common DPY19L2 mutation is the 200 kb deletion arising from a nonallelic homologous recombination (NAHR) between the flanking low copy repeats (LCRs). Here we describe the presence of a homozygous deletion of the DPY19L2 gene in two infertile Macedonian patients with 100.0% round headed spermatozoa, thus suggesting that this deletion represents a major cause of globozoospermia among Macedonian men.

De novo Unbalanced 1;22 Translocation with 22q11 Deletion Syndrome

2019 ◽  
Vol 158 (1) ◽  
pp. 32-37
Author(s):  
Spiros Vittas ◽  
George Efstathiou ◽  
Christos Tsakalidis ◽  
Christina Malamaki ◽  
Vasiliki Antari ◽  
...  
Keyword(s):  
Cytogenetic Analysis ◽  
De Novo ◽  
Velocardiofacial Syndrome ◽  
Diagnostic Methods ◽  
Chromosome 1 ◽  
Deletion Syndrome ◽  
Fish Analysis ◽  
22Q11 Deletion ◽  
Newborn Girl ◽  
Normal Fish

This report describes a newborn girl presenting with some of the common features of DiGeorge syndrome/velocardiofacial syndrome (DGS/VCFS), including hypocalcemia, atrial septal defect, and aortic stenosis. Several genetic tests were carried out to determine the origin of the clinical phenotype. MLPA was initially performed followed by aCGH, cytogenetic analysis, and FISH. Cytogenetic analysis of the proband's parents was also done. MLPA revealed a deletion in 22q11.1q11.2 spanning from the cat eye syndrome region to the most commonly deleted region in DGS/VCFS patients. The size of the deletion as defined by aCGH was 3.2 Mb. The karyotype of the proband was 45,XX,der(1)t(1;22)(p36.3;q11.2)dn,-22, the karyotypes of the parents were normal. FISH analysis showed that the 22q11 deletion occurred in the der(1). No loss or gain of chromosomal material was evident for chromosome 1, as confirmed by MLPA, aCGH, and FISH. Unbalanced translocations resulting in DGS are relatively rare, with limited reports in the literature. To our knowledge, this is the second case involving chromosome 1 and the first one with breakpoints in 1p36 and 22q11.2. This case also emphasizes the importance of combining diagnostic methods to better understand a given genetic abnormality.

Prenatal Diagnosis of 4q Terminal Deletion and Review of the Literature

2019 ◽  
Vol 158 (2) ◽  
pp. 63-73 ◽  
Author(s):  
Zsolt Tidrenczel ◽  
Erika P. Tardy ◽  
Henriett Pikó ◽  
Edina Sarkadi ◽  
Ildikó Böjtös ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
De Novo ◽  
Phenotypic Variability ◽  
Chromosome Analysis ◽  
Index Patient ◽  
Maternal Serum ◽  
Prenatal Ultrasound ◽  
Terminal Deletion ◽  
Deletion Syndrome ◽  
Comparative Genome Hybridization

Terminal deletion of chromosome 4 (4q deletion syndrome) is a rare genetic condition that is characterized by a broad clinical spectrum and phenotypic variability. Diagnosis of the distinct condition can be identified by conventional chromosome analysis and small deletions by novel molecular cytogenetic methods such as microarray comparative genome hybridization (aCGH). Prenatal diagnosis is challenging; to date 10 cases have been described. We report a prenatally diagnosed case of de novo 4q deletion syndrome confirmed by conventional karyotyping and FISH due to an elevated combined risk for Down syndrome and prenatal ultrasound findings. aCGH validated the diagnosis and offered exact characterization of the disorder. Cytogenetic and microarray results described a 4q32.1qter terminal deletion of the fetus. Prenatal ultrasound detected multiple nonstructural findings (micrognathia, choroid plexus cysts, echogenic fetal bowel, short femur, and cardiac axis deviation). Pregnancy was terminated at 20 weeks. In addition to the index patient, we reviewed the 10 prenatally published cases of 4q deletion syndrome in the literature and compared these with our results. We summarize the patients' characteristics and prenatal clinical findings. Alterations of maternal serum biochemical factors, an elevated combined risk for trisomies, and distinct ultrasonographic findings can often be observed in cases of prenatal 4q deletion syndrome and may facilitate the otherwise difficult prenatal diagnosis.

scholarly journals Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations

2012 ◽  
Vol 23 (3) ◽  
pp. 411-418 ◽  
Author(s):  
C. Robberecht ◽  
T. Voet ◽  
M. Z. Esteki ◽  
B. A. Nowakowska ◽  
J. R. Vermeesch
Keyword(s):  
Homologous Recombination ◽  
De Novo ◽  
Retrotransposable Elements ◽  
Nonallelic Homologous Recombination
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