Evaluation of a patient with classical Ehlers‐Danlos syndrome due to a 9q34 duplication affecting <i>COL5A1</i>

Kuroda, Yukiko; Ohashi, Ikuko; Naruto, Takuya; Ida, Kazumi; Enomoto, Yumi; Nagai, J.; Kurosawa, Kenji

doi:10.1111/cga.12277

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…We found that NGS can detect the CNV that were already identified in the microarray analysis (data not shown). We have shown previously that it is possible to detect CNV using NGS but not aCGH, at the exon‐level . The overall diagnostic rate of Group A was 39% (39 cases).…”

Section: Resultsmentioning

confidence: 95%

An efficient genetic test flow for multiple congenital anomalies and intellectual disability

Yokoi

Enomoto

Tsurusaki

et al. 2020

Pediatrics International

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Background: Genetic testing has enabled the diagnosis of multiple congenital anomalies and/or intellectual disabilities. However, because of the phenotypic variability in these disorders, selection of an appropriate genetic test can be difficult and complex. For clinical examination, particularly in clinical facilities, a simple and standardized system is needed. Methods: We compared microarray comparative genomic hybridization and clinical exome sequencing with regard to diagnostic yield, cost, and time required to reach a definitive diagnosis. After first performing G-banding for 200 patients with multiple congenital anomalies and/or intellectual disability, as a subsequent genetic test, microarray and clinical exome sequencing were compared with regard to diagnostic yield, cost, and time required.Results: There was no obvious difference in the diagnostic rate between the two methods; however, clinical exome sequencing was superior in terms of cost and time. In addition, clinical exome sequencing could sufficiently identify copy number variants, and even smaller copy number variants could be identified.Conclusions: Clinical exome sequencing should be implemented earlier as a genetic test for undiagnosed patients with multiple congenital anomalies and/or intellectual disabilities. Our results can be used to establish inspection methods in clinical facilities.

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Section: Resultsmentioning

confidence: 95%

An efficient genetic test flow for multiple congenital anomalies and intellectual disability

Yokoi

Enomoto

Tsurusaki

et al. 2020

Pediatrics International

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“…In Ritelli et al, an investigation among 40 patients, one of the duplications of exons 1-11 in COL5A1 was detected (probe for COL5A2 were not available) [16]. In the investigation of Kuroda et al, cEDS patients with alterations in COL5A1 (deletion of exons 2-11 and duplication of exons 12-65) were determined identified by aCGH [17]. All patients analyzed in the present study need wider diagnostics because we cannot exclude DNA changes other than those detected by NGS.…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome

Junkiert-Czarnecka

Pilarska-Deltow

Bąk

et al. 2022

CIMB

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Background: Ehlers-Danlos syndrome (EDS) is a common non-inflammatory, congenital connective tissue disorder. Classical type (cEDS) EDS is one of the more common forms, typically caused by mutations in the COL5A1 and COL5A2 genes, though causative mutations in the COL1A1 gene have also been described. Material and methods: The study group included 59 patients of Polish origin, diagnosed with cEDS. The analysis was performed on genomic DNA (gDNA) with NGS technology, using an Illumina sequencer. Thirty-five genes related to connective tissue were investigated. The pathogenicity of the detected variants was assessed by VarSome. Results: The NGS of 35 genes revealed variants within the COL5A1, COL5A2, COL1A1, and COL1A2 genes for 30 of the 59 patients investigated. Our panel detected no sequence variations for the remaining 29 patients. Discussion: Next-generation sequencing, with an appropriate multigene panel, showed great potential to assist in the diagnosis of EDS and other connective tissue disorders. Our data also show that not all causative genes giving rise to cEDS have been elucidated yet.

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“…Mutations in an X-linked gene, NEXMIF (neurite extension and migration factor, also known as KIDLIA, KIAA2022, or Xpn) were first discovered in several males with ASD, intellectual disability, and other co-morbidities (Cantagrel et al, 2004;Van Maldergem et al, 2013). Since then, several studies have reported additional ASD individuals with mutations or deletions in the NEXMIF gene (Lim et al, 2013;Iossifov et al, 2014;Charzewska et al, 2015;Kuroda et al, 2015;De Lange et al, 2016;Farach and Northrup, 2016;Webster et al, 2017;Yuen et al, 2017;Lambert et al, 2018;Lorenzo et al, 2018;Panda et al, 2020;Stamberger et al, 2020;Wang et al, 2020). NEXMIF is now recognized as a Category 1 gene in the Simons Foundation Autism Research Initiative (SFARI) database, further implicating it as an ASD-risk gene.…”

Section: Introductionmentioning

confidence: 99%

The autism spectrum disorder risk gene NEXMIF over-synchronizes hippocampal CA1 network and alters neuronal coding

Mount,

Athif,

O’Connor

et al. 2023

Front. Neurosci.

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Mutations in autism spectrum disorder (ASD) risk genes disrupt neural network dynamics that ultimately lead to abnormal behavior. To understand how ASD-risk genes influence neural circuit computation during behavior, we analyzed the hippocampal network by performing large-scale cellular calcium imaging from hundreds of individual CA1 neurons simultaneously in transgenic mice with total knockout of the X-linked ASD-risk gene NEXMIF (neurite extension and migration factor). As NEXMIF knockout in mice led to profound learning and memory deficits, we examined the CA1 network during voluntary locomotion, a fundamental component of spatial memory. We found that NEXMIF knockout does not alter the overall excitability of individual neurons but exaggerates movement-related neuronal responses. To quantify network functional connectivity changes, we applied closeness centrality analysis from graph theory to our large-scale calcium imaging datasets, in addition to using the conventional pairwise correlation analysis. Closeness centrality analysis considers both the number of connections and the connection strength between neurons within a network. We found that in wild-type mice the CA1 network desynchronizes during locomotion, consistent with increased network information coding during active behavior. Upon NEXMIF knockout, CA1 network is over-synchronized regardless of behavioral state and fails to desynchronize during locomotion, highlighting how perturbations in ASD-implicated genes create abnormal network synchronization that could contribute to ASD-related behaviors.

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Evaluation of a patient with classical Ehlers‐Danlos syndrome due to a 9q34 duplication affecting COL5A1

Cited by 4 publications

References 9 publications

An efficient genetic test flow for multiple congenital anomalies and intellectual disability

An efficient genetic test flow for multiple congenital anomalies and intellectual disability

Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome

The autism spectrum disorder risk gene NEXMIF over-synchronizes hippocampal CA1 network and alters neuronal coding

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