Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies

2020 ◽  
Vol 160 (10) ◽  
pp. 579-588
Author(s):  
Martha L. Ornelas-Arana ◽  
Guillermo Pérez-Garcia ◽  
Carla D. Robles-Espinoza ◽  
Martha M. Rangel-Sosa ◽  
Carolina Castaneda-Garcia ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Recurrence Risk ◽  
Female Child ◽  
Clinical Findings ◽  
Facial Dysmorphism ◽  
End Joining ◽  
Position Effects ◽  
Genomic Characterization

“Simple” 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailing an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including <i>LMNA</i>, <i>USF1</i>, <i>VANGL2</i>, <i>LOR</i>, and <i>POGZ</i>) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between <i>CPNE9</i> and <i>BRPF1</i>) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient’s phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness – rather than lethality issues – may account for the paucity of “simple” interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the insertion breakpoint is consistent with a simple nonhomologous end-joining mechanism, in contrast to a chromothripsis-like event, which has previously been seen in other nonrecurrent insertions. Taken together, the data gathered in this study allowed us to inform this family about the low recurrence risk but not to predict the reproductive prognosis for hypothetical carriers. We highlight that genomic-level assessment is a powerful tool that allows the visualization of the full landscape of sporadic chromosomal injuries and can be used to improve genetic counseling.

Abstract LB-236: Genomic characterization of circulating tumor cells in de novo metastatic prostate cancer

2019 ◽  
Author(s):  
Shoujie Chai ◽  
Paymaneh D. Malihi ◽  
Ana M. Apariciop ◽  
Brian F. Chapin ◽  
Matthew Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Genomic Characterization

scholarly journals Cytogenetic and Array-CGH Characterization of a Complex de novo Rearrangement Involving Duplication and Deletion of 9p and Clinical Findings in a 4-Month-Old Female

2009 ◽  
Vol 126 (3) ◽  
pp. 305-312 ◽  
Author(s):  
P.J. Hulick ◽  
K.M. Noonan ◽  
S. Kulkarni ◽  
D.J. Donovan ◽  
M. Listewnik ◽  
...  
Keyword(s):  
Array Cgh ◽  
De Novo ◽  
Clinical Findings

scholarly journals Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation

2018 ◽  
Vol 8 (8) ◽  
pp. 145 ◽  
Author(s):  
Jennifer Gardner ◽  
Thomas Cushion ◽  
Georgios Niotakis ◽  
Heather Olson ◽  
P. Grant ◽  
...  
Keyword(s):  
De Novo ◽  
Functional Characterization ◽  
Clinical Manifestations ◽  
Fetal Brain ◽  
Detailed Comparison ◽  
Hek 293 ◽  
293 Cells ◽  
Brain Malformations ◽  
Computer Based

The TUBA1A gene encodes tubulin alpha-1A, a protein that is highly expressed in the fetal brain. Alpha- and beta-tubulin subunits form dimers, which then co-assemble into microtubule polymers: dynamic, scaffold-like structures that perform key functions during neurogenesis, neuronal migration, and cortical organisation. Mutations in TUBA1A have been reported to cause a range of brain malformations. We describe four unrelated patients with the same de novo missense mutation in TUBA1A, c.5G>A, p.(Arg2His), as found by next generation sequencing. Detailed comparison revealed similar brain phenotypes with mild variability. Shared features included developmental delay, microcephaly, hypoplasia of the cerebellar vermis, dysplasia or thinning of the corpus callosum, small pons, and dysmorphic basal ganglia. Two of the patients had bilateral perisylvian polymicrogyria. We examined the effects of the p.(Arg2His) mutation by computer-based protein structure modelling and heterologous expression in HEK-293 cells. The results suggest the mutation subtly impairs microtubule function, potentially by affecting inter-dimer interaction. Based on its sequence context, c.5G>A is likely to be a common recurrent mutation. We propose that the subtle functional effects of p.(Arg2His) may allow for other factors (such as genetic background or environmental conditions) to influence phenotypic outcome, thus explaining the mild variability in clinical manifestations.

scholarly journals Cerebral White Matter Lesions and Dysmorphisms: Signs Suggestive of 6p25 Deletion Syndrome—Literature Review

2019 ◽  
Vol 08 (04) ◽  
pp. 205-211
Author(s):  
Piero Pavone ◽  
Simona Domenica Marino ◽  
Giovanni Corsello ◽  
Martino Ruggieri ◽  
Danilo Castellano Chiodo ◽  
...  
Keyword(s):  
White Matter ◽  
Developmental Delay ◽  
De Novo ◽  
Clinical Manifestations ◽  
Deletion Syndrome ◽  
Cerebral White Matter ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Perivascular Spaces ◽  
Renal Malformations

AbstractDeletion of the region including chromosome 6p25 has been defined as a syndrome, with more than 68 reported cases. Individuals affected by the syndrome exhibit variable findings, including developmental delay and intellectual disability, cardiac anomalies, dysmorphic features, and—less commonly—skeletal and renal malformations. Ocular and hearing abnormalities are the most notable presenting features. The region encompasses more than 15 genes, of which the FOX group is the most likely causal factor of the clinical manifestations. We report the case of a 2-year-old child with developmental delay, generalized hypotonia, facial dysmorphism, and anomalies involving malformations of the eyes, heart, teeth, and skeleton. The magnetic resonance imaging (MRI) of the child's brain displayed cerebral anomalies involving the white matter, perivascular spaces, and corpus callosum. Array-CGH (comparative genomic hybridization) analysis displayed a de novo partial deletion of the short arm of chromosome 6, extending 5.13 Mb from nt 407.231 to nt 5.541.179. In infancy, neuroradiologic findings of abnormalities in the cerebral white matter and other neurologic anomalies elsewhere in the brain, in association with dysmorphisms and malformations, are highly suggestive of the diagnosis of 6p25 deletion syndrome. When these anomalies are found, the syndrome must be included in the differential diagnosis of disorders affecting the cerebral white matter.

scholarly journals Cytogenetic and Array-CGH Characterization of a Simple Case of Reciprocal t(3;10) Translocation Reveals a Hidden Deletion at 5q12

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 877
Author(s):  
Angelo Cellamare ◽  
Nicoletta Coccaro ◽  
Maria Cristina Nuzzi ◽  
Paola Casieri ◽  
Marilina Tampoia ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Array Cgh ◽  
Clinical Manifestations ◽  
Postnatal Growth ◽  
Facial Dysmorphism ◽  
Conventional Cytogenetic Analysis ◽  
Wide Range ◽  
Conventional Cytogenetics ◽  
First Time

Chromosome deletions, including band 5q12, have rarely been reported and have been associated with a wide range of clinical manifestations, such as postnatal growth retardation, intellectual disability, hyperactivity, nonspecific ocular defects, facial dysmorphism, and epilepsy. In this study, we describe for the first time a child with growth retardation in which we identified a balanced t(3;10) translocation by conventional cytogenetic analysis in addition to an 8.6 Mb 5q12 deletion through array-CGH. Our results show that the phenotypic abnormalities of a case that had been interpreted as “balanced” by conventional cytogenetics are mainly due to a cryptic deletion, highlighting the need for molecular investigation in subjects with an abnormal phenotype before assuming the cause is an apparently simple cytogenetic rearrangement. Finally, we identify PDE4D and PIK3R1 genes as the two major candidates responsible for the clinical features expressed in our patient.

Do Rear-End Motor Vehicle Collisions Cause Rotator Cuff Tears?

2014 ◽  
Vol 19 (1) ◽  
pp. 3-7
Author(s):  
Charles N. Brooks ◽  
James R. Funk ◽  
J. Mark Melhorn ◽  
James B. Talmage ◽  
Christopher R. Brigham
Keyword(s):  
Rotator Cuff ◽  
Motor Vehicle ◽  
De Novo ◽  
Clinical Manifestations ◽  
High Energy ◽  
Clinical Findings ◽  
Rotator Cuff Tears ◽  
Motor Vehicle Collisions ◽  
Vehicle Collisions ◽  
Causation Analysis

Abstract The rotator cuff comprises four muscles and their tendons, the supraspinatus, infraspinatus, teres minor, and subscapularis. Rotator cuff tears (RCTs) are common and most frequently involve the supraspinatus, and usually occur through tendon rather than muscle. Clinical manifestations vary depending on the size and age of the tear, the individual's physical demands, psychosocial factors, and other variables; tears may range from the asymptomatic to large, full-thickness, and retracted tears that cause pain, weakness, and at least partial disability. Individuals involved in rear-end motor vehicle collisions (MVCs) may complain of “shoulder” pain, and magnetic resonance imaging may reveal the presence of shoulder cuff tears, high-energy trauma can cause rotator cuff tears, but the tensile forces encountered in rear-end MVCs almost certainly do not cause rotator cuff tears de novo. Because rear-end collisions and RCTs are common and often involve claims or lawsuits, physicians may be asked to assess the causation of the RCTs. Treatment should be based on clinical findings and not the results of imaging; the same applies to causation analysis: Involvement in a rear-end MVC does not establish causality for a rotator cuff tear. The medical literature is devoid of evidence indicating that rear-end collisions cause RCTs, but compelling evidence in the biomechanical literature shows that low-speed rear-end MVCs do not cause RCTs.

Abstract LB-236: Genomic characterization of circulating tumor cells in de novo metastatic prostate cancer

2019 ◽  
Author(s):  
Shoujie Chai ◽  
Paymaneh D. Malihi ◽  
Ana M. Apariciop ◽  
Brian F. Chapin ◽  
Matthew Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Genomic Characterization

Clinical and Cytogenomic Characterization of De Novo 11p14.3-p15.5 Duplication Associated with 18q23 Deletion in an Egyptian Female Infant

2020 ◽  
Author(s):  
Hanan H. Afifi ◽  
Ghada Y. El-Kamah ◽  
Alaa K. Kamel ◽  
Sally G. Abd Allah ◽  
Sayda Hammad ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Chromosomal Rearrangements ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Comparative Genomic ◽  
Septal Hypertrophy

AbstractPaternal microduplication of 11p14.3-p15.5 causes the clinical manifestations of Beckwith–Wiedemann syndrome (BWS), while microdeletion of 18q23-ter is clinically characterized by short stature, congenital malformations, and developmental delay. We describe a 15-month-old girl presenting with protruding tongue, dysmorphic facial features, moderate developmental delay, umbilical hernia, hypotonia, mild-to-moderate pulmonary hypertension, small patent ductus arteriosus, and mild ventricular septal hypertrophy. Brain magnetic resonance imaging showed mild atrophic changes. Chromosomal analysis revealed 46, XX, add(18)(q23). Fluorescence in situ hybridization using subtelomere 18q and whole chromosome painting 18 showed subtelomere deletion in 18q, and the add segment was not derived from chromosome 18. Microarray-based comparative genomic hybridization detected a 22 Mb duplication of chromosome 11p15.5p14.3 and a 3.7 Mb deletion of chromosome 18q23. The phenotype of the chromosomal rearrangements is probably resulted from a combination of dosage-sensitive genes. Our patient had clinical manifestations of both 18q deletion and BWS.

scholarly journals Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
C. S. Paththinige ◽  
N. D. Sirisena ◽  
U. G. I. U. Kariyawasam ◽  
L. P. C. Saman Kumara ◽  
V. H. W. Dissanayake
Keyword(s):  
Clinical Features ◽  
Congenital Abnormalities ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Ring Chromosome ◽  
Female Child ◽  
Facial Dysmorphism ◽  
Chromosome 4 ◽  
Talipes Equinovarus ◽  
Limb Deformities

A female child born preterm with intrauterine growth retardation and presenting with facial dysmorphism with clefts, microcephaly, limb deformities, and congenital abnormalities involving cardiovascular and urinary systems is described. Chromosomal analysis showed ade novo46,XX,r(4)(p15.3q35) karyotype. The clinical features of the patient were compared with the phenotypic characteristics of 17 previously reported cases with ring chromosome 4 and those with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are consistent with the consensus phenotype in ring chromosome 4. Patent ductus arteriosus and bilateral talipes equinovarus observed in this baby widen the phenotypic spectrum associated with ring chromosome 4.

scholarly journals Ocular Manifestations of a Novel Proximal 19p13.3 Microdeletion

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
L. Swan ◽  
D. Coman
Keyword(s):  
Short Stature ◽  
Developmental Delay ◽  
Medical Literature ◽  
De Novo ◽  
Phenotypic Variability ◽  
Clinical Manifestations ◽  
Phenotypic Heterogeneity ◽  
Facial Dysmorphism ◽  
Ocular Manifestations

Microdeletions at 19p13.3 are rarely reported in the medical literature with significant phenotypic variability. Among the reported cases, common clinical manifestations have included developmental delay, facial dysmorphism, and hypotonia. Herein we described a child with a de novo 19p13.3 microdeletion, proximal to the reported cases of 19p13.3 microdeletion/duplication, with ocular manifestations of bilateral ocular colobomata complicated with microphthalmos and cataract, associated with short stature. This case highlights the phenotypic heterogeneity of deletions in the 19p13.3 region.

Sign in / Sign up

Export Citation Format

Share Document