Trisomy 4 mosaicism: Delineation of the phenotype

Bouman, Arjan; Kevie-Kersemaekers, Anne-Marie van der; Amsterdam, Karin Huijsdens-van; Dahhan, Nordin; Knegt, Lia; Vansenne, Fleur; Cobben, Jan Maarten

doi:10.1002/ajmg.a.37522

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Presence of 2 Barr bodies from buccal smear supports interference due to X inactivation (data not shown). Clinical findings of patient 10 resemble those of mosaic trisomy 4, which include IUGR, cardiac anomalies, thumb hypoplasia/aplasia, intellectual disability, renal hypoplasia, dysplastic ears, and dysmorphic findings (Wieczorek et al, 2003;Brady et al, 2005;Bouman et al, 2016). Trisomic region on chromosome 4 is gene-rich, containing 1157 genes, including 508 OMIM genes.…”

Section: Discussionmentioning

confidence: 96%

Investigation of Genetic Causes in a Developmental Disorder: Oculoauriculovertebral Spectrum

Guleray

Koşukçu

Oğuz

et al. 2021

The Cleft Palate Craniofacial Journal

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Objective Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated. Design/Setting/Patients A cohort of 23 Turkish patients with OAVS, referred to Hacettepe University Hospital, Department of Pediatric Genetics from 2008 to 2018, was included in this study. Minimal diagnostic criteria for OAVS were considered as unilateral microtia or hemifacial microsomia with preauricular skin tag. The cohort was clinically reevaluated for craniofacial and extracranial findings. Molecular etiology was investigated using candidate gene sequencing following copy number variant (CNV) analysis. WES was also performed for 2 of the selected patients. Results Patients in the study cohort presented similar demographic and phenotypic characteristics to previously described patients in the literature except for a higher frequency of bilaterality, cardiac findings, and intellectual disability/developmental delay. CNV analysis revealed a possible genetic etiology for 3 patients (13%). Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 ( EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS. Conclusion Detailed clinical evaluation for any patient with OAVS is recommended due to a high rate of accompanying systemic findings. We further expand the existing genetic heterogeneity of OAVS by identifying several CNVs and a phenotypically overlapping disorder, MFDM.

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Section: Discussionmentioning

confidence: 96%

Investigation of Genetic Causes in a Developmental Disorder: Oculoauriculovertebral Spectrum

Guleray

Koşukçu

Oğuz

et al. 2021

The Cleft Palate Craniofacial Journal

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“…Trisomy of chromosome 4 is generally associated with spontaneous abortions [84]. However, no fewer than four cases of mosaic trisomy of chromosome 4 in liveborns characterized by phenotypic similarity have been reported [93].…”

Section: Mosaic Chromosome Abnormalitiesmentioning

confidence: 99%

Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism

Iourov

Vorsanova

Yurov

et al. 2019

Genes

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Intercellular karyotypic variability has been a focus of genetic research for more than 50 years. It has been repeatedly shown that chromosome heterogeneity manifesting as chromosomal mosaicism is associated with a variety of human diseases. Due to the ability of changing dynamically throughout the ontogeny, chromosomal mosaicism may mediate genome/chromosome instability and intercellular diversity in health and disease in a bottleneck fashion. However, the ubiquity of negligibly small populations of cells with abnormal karyotypes results in difficulties of the interpretation and detection, which may be nonetheless solved by post-genomic cytogenomic technologies. In the post-genomic era, it has become possible to uncover molecular and cellular pathways to genome/chromosome instability (chromosomal mosaicism or heterogeneity) using advanced whole-genome scanning technologies and bioinformatic tools. Furthermore, the opportunities to determine the effect of chromosomal abnormalities on the cellular phenotype seem to be useful for uncovering the intrinsic consequences of chromosomal mosaicism. Accordingly, a post-genomic review of chromosomal mosaicism in the ontogenetic and pathogenetic contexts appears to be required. Here, we review chromosomal mosaicism in its widest sense and discuss further directions of cyto(post)genomic research dedicated to chromosomal heterogeneity.

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