scholarly journals Candidate Genes Associated with Delayed Neuropsychomotor Development and Seizures in a Patient with Ring Chromosome 20

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Thiago Corrêa ◽  
Amanda Cristina Venâncio ◽  
Marcial Francis Galera ◽  
Mariluce Riegel
Keyword(s):  
Candidate Genes ◽  
Protein Interactions ◽  
Neurological Diseases ◽  
Ring Chromosome ◽  
Molecular Data ◽  
Clinical Findings ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Nucleosome Assembly ◽  
Chromosome 20

Ring chromosome 20 (r20) is characterized by intellectual impairment, behavioral disorders, and refractory epilepsy. We report a patient presenting nonmosaic ring chromosome 20 followed by duplication and deletion in 20q13.33 with seizures, delayed neuropsychomotor development and language, mild hypotonia, low weight gain, and cognitive deficit. Chromosomal microarray analysis (CMA) enabled us to restrict a chromosomal segment and thus integrate clinical and molecular data with systems biology. With this approach, we were able to identify candidate genes that may help to explain the consequences of deletions in 20q13.33. In our analysis, we observed five hubs (ARFGAP1, HELZ2, COL9A3, PTK6, and EEF1A2), seven bottlenecks (CHRNA4, ARFRP1, GID8, COL9A3, PTK6, ZBTB46, and SRMS), and two H-B nodes (PTK6 and COL9A3). The candidate genes may play an important role in the developmental delay and seizures observed in r20 patients. Gene ontology included microtubule-based movement, nucleosome assembly, DNA repair, and cholinergic synaptic transmission. Defects in these bioprocesses are associated with the development of neurological diseases, intellectual disability, neuropathies, and seizures. Therefore, in this study, we can explore molecular cytogenetic data, identify proteins through network analysis of protein-protein interactions, and identify new candidate genes associated with the main clinical findings in patients with 20q13.33 deletions.

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

2018 ◽  
Vol 154 (4) ◽  
pp. 201-208 ◽  
Author(s):  
Shu Liu ◽  
Zhiqing Wang ◽  
Sisi Wei ◽  
Jinqun Liang ◽  
Nuan Chen ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Gray Matter ◽  
De Novo ◽  
Ring Chromosome ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosome 6 ◽  
Material Loss ◽  
Ring Chromosome 6

Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

Ring Chromosome 9 and Chromosome 9p Deletion Syndrome in a Patient Associated with Developmental Delay: A Case Report and Review of the Literature

2016 ◽  
Vol 148 (2-3) ◽  
pp. 165-173 ◽  
Author(s):  
Aswini Sivasankaran ◽  
Murthy K. Kanakavalli ◽  
Deenadayalu Anuradha ◽  
Chandra R. Samuel ◽  
Lakshmi R. Kandukuri
Keyword(s):  
Developmental Delay ◽  
Heart Defects ◽  
Ring Chromosome ◽  
Chromosome 9 ◽  
Deletion Syndrome ◽  
Chromosomal Microarray ◽  
Facial Dysmorphism ◽  
Chromosomal Microarray Analysis ◽  
Ring Chromosomes ◽  
Normal Fish

Ring chromosomes have been described for all human chromosomes and are typically associated with physical and/or mental abnormalities resulting from a deletion of the terminal ends of both chromosome arms. This report describes the presence of a ring chromosome 9 in a 2-year-old male child associated with developmental delay. The proband manifested a severe phenotype comprising facial dysmorphism, congenital heart defects, and seizures. The child also exhibited multiple cell lines with mosaic patterns of double rings, a dicentric ring and loss of the ring associated with mitotic instability and dynamic tissue-specific mosaicism. His karyotype was 46,XY,r(9)(p22q34)[89]/46,XY,dic r(9; 9)(p22q34;p22q34)[6]/45, XY,-9[4]/47,XY,r(9),+r(9)[1]. However, the karyotypes of his parents and elder brother were normal. FISH using mBAND probe and subtelomeric probes specific for p and q arms for chromosome 9 showed no deletion in any of the regions. Chromosomal microarray analysis led to the identification of a heterozygous deletion of 15.7 Mb from 9p22.3 to 9p24.3. The probable role of the deleted genes in the manifestation of the phenotype of the proband is discussed.

Clinical findings in a patient mosaic for a supernumerary ring chromosome 20

2000 ◽  
Vol 91 (3) ◽  
pp. 171-174 ◽  
Author(s):  
Enrique Daniel Austin-Ward ◽  
Silvia Castillo ◽  
Yuri Dragnic ◽  
Patricia Sanz ◽  
Samuel Salazar ◽  
...  
Keyword(s):  
Ring Chromosome ◽  
Clinical Findings ◽  
Chromosome 20

A Revisited Diagnosis of Collagen VI Related Muscular Dystrophy in a Patient with a Novel COL6A2 Variant and 21q22.3 Deletion

2020 ◽  
Vol 51 (06) ◽  
pp. 445-449
Author(s):  
Pelin Ozlem Simsek-Kiper ◽  
Sumeyra Oguz ◽  
Fatma Bilge Ergen ◽  
Gulen Eda Utine ◽  
Mehmet Alikasifoglu ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Muscle Weakness ◽  
Ring Chromosome ◽  
Pathogenic Variant ◽  
Chromosome 21 ◽  
Muscular Dystrophies ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Collagen Vi ◽  
Genomic Deletions

AbstractThe genetic etiology of collagen VI related muscular dystrophies is heterogenous. Genomic deletions in one allele involving COL6A2 or both COL6A1 and COL6A2 unmasking a pathogenic variant in the second nondeleted allele have been described in the etiology. We aimed to report the clinical and molecular findings of a 13-year-old boy with ring chromosome 21 who presented to our clinic with easy fatigability, muscle weakness, and waddling gait. Phenotypic delineation along with chromosomal microarray analysis and DNA sequencing were performed. Affymetrix CytoScan Optima array platform and DNA sequencing revealed a 2,202 kb de novo deletion at 21q22.3, including COL6A1 and COL6A2, and a novel heterozygous variant at position c.2875G > A;p.(Glu959Lys) in COL6A2, respectively. Before his admission to our center, the patient was evaluated for hypotonia elsewhere when he was 15 months old. He was diagnosed with ring chromosome 21 on peripheral blood karyotype analysis; however, no further assessment was performed at that time. He had normal growth with mild dysmorphic facial features, distal laxity, gastrocnemius hypertrophy, proximal muscle weakness, increased lordotic posture with mild flexion contractures at the knees, and gait disturbance. Although the phenotype does not fit into classical Ullrich congenital muscular dystrophies, muscle magnetic resonance imaging (MRI) revealed a complementary pattern consistent with collagen VI related myopathies. Genetic testing confirmed the clinical diagnosis as well. This patient yet represents another example of the effect of large genomic deletions leading to recessive disorders through unmasking a pathogenic variant in the second nondeleted allele.

scholarly journals An Apparently Balanced Complex Chromosome Rearrangement Involving Seven Breaks and Four Chromosomes in a Healthy Female and Segregation/Recombination in Her Affected Son

2021 ◽  
pp. 1-9
Author(s):  
Ana Eduarda Campos ◽  
Carla Rosenberg ◽  
Ana Krepischi ◽  
Marina França ◽  
Vanessa Lopes ◽  
...  
Keyword(s):  
Chromosome Rearrangement ◽  
Clinical History ◽  
Clinical Findings ◽  
Chromosome 1 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Balanced Translocation ◽  
Phenotypic Effect ◽  
Complex Chromosome Rearrangement ◽  
Complex Chromosome

Duplication of the distal 1q and 4p segments are both characterized by the presence of intellectual disability/neurodevelopmental delay and dysmorphisms. Here, we describe a male with a complex chromosome rearrangement (CCR) presenting with overlapping clinical findings between these 2 syndromes. In order to better characterize this CCR, classical karyotyping, FISH, and chromosomal microarray analysis were performed on material from the patient and his parents, which revealed an unbalanced karyotype with duplications at 1q41q43 and 4p15.2p14 in the proband. The rearrangements, which were derived from a maternal balanced karyotype, included an insertion of a segment from the long to the short arm of chromosome 1, a balanced translocation involving chromosomes 14 and 18, and an insertion of a segment from the short arm of chromosome 4 into the derived chromosome 14. This study aimed to better define the clinical history and prognosis of a patient with this rare category of chromosomal aberration. Our results suggest that the frequency of CCR in the general population may be underestimated; when balanced, they may not have a phenotypic effect. Moreover, they emphasize the need for cytogenetic techniques complementary to chromosomal microarray for proper genetic counseling.

scholarly journals Clinical Findings Associated with a De Novo Partial Trisomy 10p11.22p15.3 and Monosomy 7p22.3 Detected by Chromosomal Microarray Analysis

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Omid Kohannim ◽  
Jane Peredo ◽  
Katrina M. Dipple ◽  
Fabiola Quintero-Rivera
Keyword(s):  
Similar Case ◽  
De Novo ◽  
Case Reports ◽  
Partial Trisomy ◽  
Bioinformatic Analysis ◽  
Clinical Findings ◽  
Chromosomal Microarray ◽  
Facial Features ◽  
Chromosomal Microarray Analysis ◽  
Segmental Aneuploidy

We present the case of an 18-month-old boy with dysmorphic facial features, developmental delay, growth retardation, bilateral clubfeet, thrombocytopenia, and strabismus, whose array CGH analysis revealed concurrentde novotrisomy 10p11.22p15.3 and monosomy 7p22.3. We describe the patient's clinical presentation, along with his cytogenetic analysis, and we compare the findings to those of similar case reports in the literature. We also perform a bioinformatic analysis in the chromosomal regions of segmental aneuploidy to find genes that could potentially explain the patient's phenotype.

scholarly journals MLPA is a practical and complementary alternative to CMA for diagnostic testing in patients with autism spectrum disorders and identifying new candidate CNVs associated with autism

PeerJ ◽  
2019 ◽  
Vol 6 ◽  
pp. e6183 ◽  
Author(s):  
Pavlina Capkova ◽  
Josef Srovnal ◽  
Zuzana Capkova ◽  
Katerina Staffova ◽  
Vera Becvarova ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Diagnostic Testing ◽  
Copy Number Variants ◽  
Ring Chromosome ◽  
Autism Spectrum ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Rare Cnvs ◽  
Pathogenic Variants ◽  
Dependent Probe

Background Autism spectrum disorder (ASD) is a complex heterogeneous developmental disease with a significant genetic background that is frequently caused by rare copy number variants (CNVs). Microarray-based whole-genome approaches for CNV detection are widely accepted. However, the clinical significance of most CNV is poorly understood, so results obtained using such methods are sometimes ambiguous. We therefore evaluated a targeted approach based on multiplex ligation-dependent probe amplification (MLPA) using selected probemixes to detect clinically relevant variants for diagnostic testing of ASD patients. We compare the reliability and efficiency of this test to those of chromosomal microarray analysis (CMA) and other tests available to our laboratory. In addition, we identify new candidate genes for ASD identified in a cohort of ASD-diagnosed patients. Method We describe the use of MLPA, CMA, and karyotyping to detect CNV in 92 ASD patients and evaluate their clinical significance. Result Pathogenic and likely pathogenic mutations were identified by CMA in eight (8.07% of the studied cohort) and 12 (13.04%) ASD patients, respectively, and in eight (8.07%) and four (4.35%) patients, respectively, by MLPA. The detected mutations include the 22q13.3 deletion, which was attributed to ring chromosome 22 formation based on karyotyping. CMA revealed a total of 91 rare CNV in 55 patients: eight pathogenic, 15 designated variants of unknown significance (VOUS)—likely pathogenic, 10 VOUS—uncertain, and 58 VOUS—likely benign or benign. MLPA revealed 18 CNV in 18 individuals: eight pathogenic, four designated as VOUS—likely pathogenic, and six designated as VOUS—likely benign/benign. Rare CNVs were detected in 17 (58.62%) out of 29 females and 38 (60.32%) out of 63 males in the cohort. Two genes, DOCK8 and PARK2, were found to be overlapped by CNV designated pathogenic, VOUS—likely pathogenic, or VOUS—uncertain in multiple patients. Moreover, the studied ASD cohort exhibited significant (p < 0.05) enrichment of duplications encompassing DOCK8. Conclusion Multiplex ligation-dependent probe amplification and CMA yielded concordant results for 12 patients bearing CNV designated pathogenic or VOUS—likely pathogenic. Unambiguous diagnoses were achieved for eight patients (corresponding to 8.7% of the total studied population) by both MLPA and CMA, for one (1.09%) patient by karyotyping, and for one (1.09%) patient by FRAXA testing. MLPA and CMA thus achieved identical reliability with respect to clinically relevant findings. As such, MLPA could be useful as a fast and inexpensive test in patients with syndromic autism. The detection rate of potentially pathogenic variants (VOUS—likely pathogenic) achieved by CMA was higher than that for MLPA (13.04% vs. 4.35%). However, there was no corresponding difference in the rate of unambiguous diagnoses of ASD patients. In addition, the results obtained suggest that DOCK8 may play a role in the etiology of ASD.

Dramatic Onset of Focal Seizures: Differentiating Structural Focal Epilepsy from Ring Chromosome 20

2017 ◽  
Vol 48 (S 01) ◽  
pp. S1-S45
Author(s):  
A. Herting ◽  
T. Cloppenborg ◽  
A. Hofmann-Peters ◽  
T. Polster
Keyword(s):  
Focal Epilepsy ◽  
Ring Chromosome ◽  
Focal Seizures ◽  
Chromosome 20

Probing the 14-3-3 Isoform-Specificity Profile of Interactions Stabilized by Fusicoccin A

2020 ◽  
Author(s):  
James Frederich ◽  
Ananya Sengupta ◽  
Josue Liriano ◽  
Ewa A. Bienkiewicz ◽  
Brian G. Miller
Keyword(s):  
Protein Interactions ◽  
Neurological Diseases ◽  
Adapter Proteins ◽  
Protein Protein Interactions ◽  
Specific Expression ◽  
Individual Client ◽  
Isoform Specificity ◽  
Fusicoccin A

Fusicoccin A (FC) is a fungal phytotoxin that stabilizes protein–protein interactions (PPIs) between 14-3-3 adapter proteins and their phosphoprotein interaction partners. In recent years, FC has emerged as an important chemical probe of human 14-3-3 PPIs implicated in cancer and neurological diseases. These previous studies have established the structural requirements for FC-induced stabilization of 14-3-3·client phosphoprotein complexes; however, the effect of different 14-3-3 isoforms on FC activity has not been systematically explored. This is a relevant question for the continued development of FC variants because there are seven distinct isoforms of 14-3-3 in humans. Despite their remarkable sequence and structural similarities, a growing body of experimental evidence supports both tissue-specific expression of 14-3-3 isoforms and isoform-specific functions <i>in vivo</i>. Herein, we report the isoform-specificity profile of FC <i>in vitro</i>using recombinant human 14-3-3 isoforms and a focused library of fluorescein-labeled hexaphosphopeptides mimicking the C-terminal 14-3-3 recognition domains of client phosphoproteins targeted by FC in cell culture. Our results reveal modest isoform preferences for individual client phospholigands and demonstrate that FC differentially stabilizes PPIs involving 14-3-3s. Together, these data provide strong motivation for the development of non-natural FC variants with enhanced selectivity for individual 14-3-3 isoforms.

Sign in / Sign up

Export Citation Format

Share Document