17q21.31 Microdeletion: Brain Anomalies Leading to Prenatal Diagnosis

Egloff, M.; Encha‐Razavi, Férechté; Garel, Catherine; Bonnière-Darcy, Maryse; Millischer, Anne-Élodie; Lapierre, Jean-Michel; Fontaine, S.; Blois, Marie‐Christine de; Vekemans, Michel; Turleau, C; Ville, Y.; Malan, Valérie

doi:10.1159/000369117

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…Deletions of this region or KANSL1 mutations lead to Koolen‐de Vries syndrome (KDVS, MIM 610443), characterized by intellectual disability, hypotonia, friendly demeanor, recognizable dysmorphic features, and less frequently cardiac or genitourinary anomalies and seizures. One of our fetal cases was reported (Egloff et al, ) It is noteworthy that a CCM is observed in 20% of deleted patients, while KDVS patients with KANSL1 mutations do not present a CCM (Zollino et al, ; Koolen et al, ). This suggests that another gene within the deletion might be responsible for this endophenotype.…”

Section: Resultsmentioning

confidence: 86%

Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation

Alby

Malan

Boutaud

et al. 2015

Birth Defects Research

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BACKGROUND: Corpus callosum malformation (CCM) is the most frequent brain malformation observed at birth. Because CCM is a highly heterogeneous condition, the prognosis of fetuses diagnosed prenatally remains uncertain, making prenatal counseling difficult. METHODS AND RESULTS: We evaluated retrospectively a total of 138 fetuses, 117 with CCM observed on prenatal imaging examination, and 21 after postmortem autopsy. On ultrasound and/or magnetic resonance imaging, CCM was either isolated (N 5 40) or associated with other neurological (N 5 57) or extra cerebral findings (N 5 21/20, respectively). RESULTS: Most fetuses (N 5 132) remained without a diagnosis at the time of pregnancy termination. This emphasizes the need to establish a neuropathological classification and to perform a genomic screening using comparative genomic hybridization. A neuropathological examination performed on 138 cases revealed a spectrum of CCMs, classified as follows: agenesis of corpus callosum (55), CC hypoplasia (30), CC dysmorphism (24), and CCM associated with a malformation of cortical development (29). Of interest, after fetopathological examination, only 16/40 malformations were classified as isolated, highlighting the importance of the autopsy following termination of pregnancy. Among the 138 cases, the underlying etiology was found in 46 cases: diabetes (one case), cytomegalovirus infection (one case), 23 chromosome abnormalities, and 21 mendelian conditions. CONCLUSION: In our series of 138 cases of CCM, prenatal and postmortem examinations identified a variety of genetic causes. However, no diagnosis could be established in 67% of cases. The classification based on the underlying neurodevelopmental defects paves the way for further genetic studies and genotype-phenotype correlations.

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Section: Resultsmentioning

confidence: 86%

Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation

Alby

Malan

Boutaud

et al. 2015

Birth Defects Research

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“…Such genes are themselves very polymorphic [60] and the different alleles allow for a fine-tuning of the immunological response. Locus 17q21.31 contains several genes potentially implicated in neurodegenerative diseases [61] and strongly tied to other dementias [62, 63]. Due to its structure, it is prone to genomic rearrangements [64, 65] whose evolutionary meaning is not yet clear.…”

Section: Resultsmentioning

confidence: 99%

Impact of polymorphic transposable elements on transcription in lymphoblastoid cell lines from public data

et al. 2019

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BackgroundTransposable elements (TEs) are DNA sequences able to mobilize themselves and to increase their copy-number in the host genome. In the past, they have been considered mainly selfish DNA without evident functions. Nevertheless, currently they are believed to have been extensively involved in the evolution of primate genomes, especially from a regulatory perspective. Due to their recent activity they are also one of the primary sources of structural variants (SVs) in the human genome. By taking advantage of sequencing technologies and bioinformatics tools, recent surveys uncovered specific TE structural variants (TEVs) that gave rise to polymorphisms in human populations. When combined with RNA-seq data this information provides the opportunity to study the potential impact of TEs on gene expression in human.ResultsIn this work, we assessed the effects of the presence of specific TEs in cis on the expression of flanking genes by producing associations between polymorphic TEs and flanking gene expression levels in human lymphoblastoid cell lines. By using public data from the 1000 Genome Project and the Geuvadis consortium, we exploited an expression quantitative trait loci (eQTL) approach integrated with additional bioinformatics data mining analyses. We uncovered human loci enriched for common, less common and rare TEVs and identified 323 significant TEV-cis-eQTL associations. SINE-R/VNTR/Alus (SVAs) resulted the TE class with the strongest effects on gene expression. We also unveiled differential functional enrichments on genes associated to TEVs, genes associated to TEV-cis-eQTLs and genes associated to the genomic regions mostly enriched in TEV-cis-eQTLs highlighting, at multiple levels, the impact of TEVs on the host genome. Finally, we also identified polymorphic TEs putatively embedded in transcriptional units, proposing a novel mechanism in which TEVs may mediate individual-specific traits.ConclusionWe contributed to unveiling the effect of polymorphic TEs on transcription in lymphoblastoid cell lines.

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“…The central nervous system abnormalities include ventriculomegaly, anomalies of corpus callosum, white matter abnormalities, etc. (Egloff et al, 2014). None of these structural malformations were found in our patients.…”

Section: Discussionmentioning

confidence: 99%

Koolen‐de Vries syndrome: First report of two unrelated Indian patients

Saxena

Moirangthem

Shambhavi

et al. 2020

American J of Med Genetics Pt A

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Koolen‐de Vries syndrome is a recurrent microdeletion syndrome caused due to deletion of around 400–600 kb region at 17q21.31. The deleted region contains various genes including KANSL1 and individuals with KANSL1 sequence variations and similar phenotypic manifestations have also been described. It is characterized by typical facial features, variable degree of intellectual disability, seizures, and behavioral problems. Here, we describe the phenotypic features of two patients and to the best of our knowledge, this is the first case report of Koolen‐de Vries syndrome from India.

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17q21.31 Microdeletion: Brain Anomalies Leading to Prenatal Diagnosis

Cited by 11 publications

References 20 publications

Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation

Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation

Impact of polymorphic transposable elements on transcription in lymphoblastoid cell lines from public data

Koolen‐de Vries syndrome: First report of two unrelated Indian patients

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