Genomic structural variants are linked with intellectual disability

Bulayeva, Kazima; Lesch, Klaus‐Peter; Bulayev, Oleg; Walsh, Christopher A.; Glatt, Stephen J.; Gurgenova, Farida; Omarova, Jamilja; Berdichevets, Irina; Thompson, Paul M.

doi:10.1007/s00702-015-1366-8

Cited by 21 publications

(16 citation statements)

References 42 publications

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“…However, based on the most recent summary of DEAF1 patients, these patients have a more severe motor delay, severe delay in expressive speech (absent speech to ten single words), and very severe intellectual disability compared with our patient . Closer examination of the MED13L haploinsufficiency syndrome phenotype, through analyzing the 21 known reported MED13L variant cases , showed that our patient is similar to other MED13L haploinsufficiency cases (Table ). Further, similar missense mutations of MED13L that occur later in the protein in the C‐terminal region have a milder phenotype in terms of ID and language development .…”

Section: Resultssupporting

confidence: 58%

Coupling clinical exome sequencing with functional characterization studies to diagnose a patient with familial Mediterranean fever and MED13L haploinsufficiency syndromes

Mullegama

Jensik

et al. 2017

Clinical Case Reports

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Section: Resultssupporting

confidence: 58%

Coupling clinical exome sequencing with functional characterization studies to diagnose a patient with familial Mediterranean fever and MED13L haploinsufficiency syndromes

Mullegama

Jensik

et al. 2017

Clinical Case Reports

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“…41 Also, CDK2AP1 in the yellow module was recently identified as a susceptibility gene for intellectual disability. 42 Alsayegh et al have also shown that CDK2AP1 gene was associated with the differentiation of human embryonic stem cells and the percentage of cells in the S phase. 43 On the other hand, Manolio et al reported that the cumulative effect of rare variants, especially genes regulating immune activation, may influence brain structure and neurodevelopment deficit in patients with schizophrenia as well as account for the part of 'missing heritability' in schizophrenia.…”

Section: Discussionmentioning

confidence: 97%

Genes in immune pathways associated with abnormal white matter integrity in first-episode and treatment-naïve patients with schizophrenia

et al. 2019

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BackgroundPrevious studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.AimsTo detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.MethodThe analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.ResultsPatients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.ConclusionsThe pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.Declaration of interestsNone.

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“…Given that most similar patients had male genitalia abnormalities, the authors suggested that the TESC gene was crucial for the defective development (Al-Zahrani et al, 2011). TESC mutations are also present among the genes associated with intellectual disability in a cohort of psychiatric patients in the Dagestan region of southern Russia (Bulayeva et al, 2015).…”

Section: Subcellular Localization and Tissue Distribution Of Tescalcinmentioning

confidence: 99%

Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation

Kolobynina

Solovyova

Levay

et al. 2016

Journal of Cell Science

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Tescalcin (TESC, also known as calcineurin-homologous protein 3, CHP3) is a 24-kDa EF-hand Ca2+-binding protein that has recently emerged as a regulator of cell differentiation and growth. The TESC gene has also been linked to human brain abnormalities, and high expression of tescalcin has been found in several cancers. The expression level of tescalcin changes dramatically during development and upon signal-induced cell differentiation. Recent studies have shown that tescalcin is not only subjected to up- or down-regulation, but also has an active role in pathways that drive cell growth and differentiation programs. At the molecular level, there is compelling experimental evidence showing that tescalcin can directly interact with and regulate the activities of the Na+/H+ exchanger NHE1, subunit 4 of the COP9 signalosome (CSN4) and protein kinase glycogen-synthase kinase 3 (GSK3). In hematopoetic precursor cells, tescalcin has been shown to couple activation of the extracellular signal-regulated kinase (ERK) cascade to the expression of transcription factors that control cell differentiation. The purpose of this Commentary is to summarize recent efforts that have served to characterize the biochemical, genetic and physiological attributes of tescalcin, and its unique role in the regulation of various cellular functions.

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Genomic structural variants are linked with intellectual disability

Cited by 21 publications

References 42 publications

Coupling clinical exome sequencing with functional characterization studies to diagnose a patient with familial Mediterranean fever and MED13L haploinsufficiency syndromes

Coupling clinical exome sequencing with functional characterization studies to diagnose a patient with familial Mediterranean fever and MED13L haploinsufficiency syndromes

Genes in immune pathways associated with abnormal white matter integrity in first-episode and treatment-naïve patients with schizophrenia

Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation

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