Brain white matter abnormalities associated with copy number variants

Vigdorovich, Nitzan; Ben-Sira, Liat; Blumkin, Lubov; Precel, Ronit; Nezer, Ifat; Yosovich, Keren; Cross, Zachary; Vanderver, Adeline; Lev, Dorit; Lerman‐Sagie, Tally; Zerem, Ayelet

doi:10.1002/ajmg.a.61389

Cited by 7 publications

(9 citation statements)

References 42 publications

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“…Brain MRI showed defective white matter myelination for age in our proband. This finding is consistent with Vigdorovich et al [2020] who emphasized that micro-rearrangement syndromes including 1p36 deletion syndrome should be considered in patients with delayed myelination or hypomyelination of white matter. Although monosomy 1p36 is a clinically recognizable syndrome, phenotypic differences are frequently detected between patients.…”

Section: Discussionsupporting

confidence: 89%

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

et al. 2020

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Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.

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Section: Discussionsupporting

confidence: 89%

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

et al. 2020

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“…We now know that brain images that mimic HIE can be seen in some microdeletion/microduplication disorders. 3 All the microdeletions and microduplications (only studied since 2005), as well as the chromosome abnormalities listed in Table 1, were found after the birth of a child with claimed HIE. Parental microarrays were mostly not carried out, and the significance of deletions/duplications often not proven because of legal strategies.…”

Section: Discussionmentioning

confidence: 99%

Obstetrics, genetics, and litigation

Milunsky

2021

Acta Obstet Gynecol Scand

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Claims of medical malpractice are universal as reflected by reports from many countries. The fact that no departure from an expected standard of care occurred is often overlooked, ignored, or lost in the welter of grief. Not infrequently and often years later, in a majority of malpractice claims, there is vindication via a defense verdict of the rendered care, but not without considerable physician pain, cost, and embarrassment.Advances in human genetics have increasingly enabled detection of previously unrecognized genetic disorders that caused or contributed to adverse pregnancy outcome. Months to many years may elapse before a precise diagnosis is made, sometimes even after a settlement or verdict is reached. Genetic disorder, congenital

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“…Determination of deletion or duplication in patients with CNV increased the risk of myelination disorders 4.77-fold compared to the normal group. Vigdorovich et al (37), also determined that different chromosomal micro-rearrangement syndromes create nonspecific multifocal and especially periventricular white matter changes as a common feature at CMRI. The authors also reported that these lesions may also be accompanied by corpus callosum dysgenesis or gray matter loss.…”

Section: Discussionmentioning

confidence: 99%

Pediatrik Nörolojide Klinik Fenotipler ve Kromozomal Mikrodelesyon/Duplikasyonlar Arasındaki İlişki

Türay

Eröz

Habiloğlu

et al. 2021

Düzce Tıp Fakültesi Dergisi

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Aim:The aim of this study was to determine the diagnostic utility of chromosomal microarray analysis (CMA) in daily pediatric neurology practice and to identify the guiding clinical parameters for patients requiring this test. Material and Methods: The CMA results for 91 patients with global developmental delay/intellectual disability (GDD/ID) admitted to our pediatric neurology clinic for various reasons between 2018 and 2020 were examined. Demographical and clinical data for 34 patients (37.4%) in whom del/dup was determined at CMA and 57 patients (62.6%) with normal CMA were compared. Results: There was no statistically significant difference between two groups in terms of demographic characteristics such as age, gender, type of delivery, gestational age, etc. Dysmorphisms, hypotonia, myelination abnormalities were significantly more frequent in patients with del/dup than in patients with normal result. The frequency of macrocephaly and obesity was higher in the normal group, and that of generalized seizures was higher among epileptic patients in this group. Nineteen (55.9%) of the 34 cases who have del/dup detected at analysis were regarded as pathogenic, 15 (44.1%) as uncertain clinical significance (likely pathogenic, likely benign and no subclassification). Conclusion: Since CMA is an expensive, laborious, and time-consuming test, considering clinical parameters when requesting CMA will yield high diagnostic efficiency. A high possibility of copy number variants may be predicted in GDD/ID patients with dysmorphisms, hypotonia, and myelination delay. CMA should represent the genetic analysis of choice in pediatric neurology practice in case of no finding suggesting a different etiology in these patients.

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Brain white matter abnormalities associated with copy number variants

Cited by 7 publications

References 42 publications

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

Obstetrics, genetics, and litigation

Pediatrik Nörolojide Klinik Fenotipler ve Kromozomal Mikrodelesyon/Duplikasyonlar Arasındaki İlişki

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