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

Terminal deletions in the long arm of chromosome 4 are an uncommon event, with a worldwide incidence of approximately 0.001%. The majority of these deletions occur de novo. Terminal deletion cases are usually accompanied by clinical findings that include facial and cardiac anomalies, as well as intellectual disability. In this study, we describe the case of a 2-year-old girl, the fourth child born to consanguineous parents. While her karyotype was normal, a homozygous deletion was identified in the chromosome 4q35.2 region by subtelomeric FISH. A heterozygous deletion of the chromosome 4q35.2 region was observed in both parents. According to the literature, this is the first report of a case that has inherited a homozygous deletion of chromosome 4qter from carrier parents. Subsequent array-CGH analyses were performed on both the case and her parents. Whole-exome sequencing was also carried out to determine potential variants. We detected a NM_001111125.3:c.2329G>T (p.Glu777Ter) nonsense variant of the IQSEC2 gene in the girl, a variant that is related to X-linked intellectual disability.

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FISH and array CGH characterization of de novo derivative Y chromosome (Yq duplication and partial Yp deletion) in an azoospermic male

Reproductive BioMedicine Online ◽

10.1016/j.rbmo.2015.04.014 ◽

2015 ◽

Vol 31 (2) ◽

pp. 217-224 ◽

Cited By ~ 3

Author(s):

Ewa Wiland ◽

Alexander N. Yatsenko ◽

Archana Kishore ◽

Halina Stanczak ◽

Agata Zdarta ◽

...

Keyword(s):

Y Chromosome ◽

Array Cgh ◽

De Novo

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

Cytogenetic and Genome Research ◽

10.1159/000511234 ◽

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 LMNA, USF1, VANGL2, LOR, and POGZ) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between CPNE9 and BRPF1) 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.

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Clinical and Molecular Cytogenetic Characterization of a de novo Interstitial 1p31.1p31.3 Deletion in a Boy with Moderate Intellectual Disability and Severe Language Impairment

Cytogenetic and Genome Research ◽

10.1159/000431391 ◽

2015 ◽

Vol 146 (1) ◽

pp. 39-43 ◽

Cited By ~ 7

Author(s):

Elisa Tassano ◽

Alessandra Gamucci ◽

Maria E. Celle ◽

Patrizia Ronchetto ◽

Cristina Cuoco ◽

...

Keyword(s):

Intellectual Disability ◽

Language Impairment ◽

Array Cgh ◽

De Novo ◽

Phenotype Correlation ◽

Molecular Cytogenetic ◽

Genotype Phenotype Correlation ◽

Cytogenetic Characterization ◽

Inducible Gene

Interstitial 1p deletions are rare events. Very few cases of 1p31.1p31.3 deletions characterized by variable phenotypes have been reported. No clear genotype-phenotype correlation has been determined yet. We present a child with a de novo interstitial 1p31.1p31.3 deletion, identified by array CGH, associated with intellectual disability and severe language impairment. The deleted region contains 20 OMIM genes, but we focused on GADD45A (MIM 126335; growth arrest- and DNA damage-inducible gene), LRRC7 (MIM 614453; leucine-rich repeat-containing protein 7), and NEGR1 (MIM 613173; neuronal growth regulator 1). We discuss whether these genes play a role in determining the phenotype of our patient in order to investigate the possibility of a genotype-phenotype correlation.

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Array-CGH characterization of a de novo t(X;Y)(p22;q11) in a female with short stature and mental retardation

Gene ◽

10.1016/j.gene.2012.05.009 ◽

2012 ◽

Vol 504 (1) ◽

pp. 107-110 ◽

Cited By ~ 6

Author(s):

Chiara Palka-Bayard-de-Volo ◽

Stefania De Marco ◽

Valentina Chiavaroli ◽

Melissa Alfonsi ◽

Giuseppe Calabrese ◽

...

Keyword(s):

Mental Retardation ◽

Short Stature ◽

Array Cgh ◽

De Novo

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Cytogenetic and array CGH characterization of de novo 1p36 duplications and deletion in a patient with congenital cataracts, hearing loss, choanal atresia, and mental retardation

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.32437 ◽

2008 ◽

Vol 146A (21) ◽

pp. 2785-2790 ◽

Cited By ~ 11

Author(s):

Emily Chen ◽

Elise Obolensky ◽

Katherine A. Rauen ◽

Lisa G. Shaffer ◽

Xu Li

Keyword(s):

Hearing Loss ◽

Mental Retardation ◽

Array Cgh ◽

De Novo ◽

Choanal Atresia ◽

Congenital Cataracts

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Characterization of a de novo Supernumerary Neocentric Ring Chromosome Derived from Chromosome 7

Cytogenetic and Genome Research ◽

10.1159/000442265 ◽

2015 ◽

Vol 147 (2-3) ◽

pp. 111-117 ◽

Cited By ~ 3

Author(s):

Camille Louvrier ◽

Grégory Egea ◽

Audrey Labalme ◽

Vincent Des Portes ◽

Sophie Gazzo ◽

...

Keyword(s):

Array Cgh ◽

De Novo ◽

Ring Chromosome ◽

Partial Trisomy ◽

Complete Characterization ◽

Chromosome 7 ◽

Oligonucleotide Array ◽

Facial Dysmorphism ◽

Bioinformatic Tools

Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype.

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