Abstract:
BACKGROUND:Epilepsy belongs to a group of chronic and highly heterogeneous brain disorders. Many types of epilepsy and epileptic syndromes are caused by genetic factors. The neural amino acid y-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system. It regulates activity of channel pores by binding to transmembrane GABA-receptors (GABRs). The GABRs are heteropentamers assembled from different receptor subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3). Several epileptic disorders are caused by mutations in genes encoding single GABRs. METHODS:We applied trio- and single-whole exome sequencing to search for genetic sequence variants associated with a wide range of epileptic phenotypes accompanied by intellectual disability and/or global developmental delay in the investigated patients. RESULTS:We identified four hemizygous sequence variants in the GABAA receptor subunit ε gene (GABRE), including one nonsense (NM_004961.3: c.399C>A, p.Tyr133*), two missense variants (NM_004961.3: c.664G>A, p.Glu222Lys; NM_004961.3: c.1045G>A, p.Val349Ile), and one variant affecting the translation initiation codon (NM_004961.3: c.1A>G, p.Met1?) in four unrelated families. CONCLUSION:Our clinical and molecular genetic findings suggest that GABRE is a likely candidate gene for epilepsy. Nevertheless, functional studies are necessary to better understand pathogenicity of the GABRE-mutations and their associations with epileptic phenotypes.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Markus F,Angelini C,Trimouille A,Rudolf G,Lesca G,Goizet C,Lasseaux E,Arveiler B,van Slegtenhorst M,Brooks AS,Abou Jamra R,Korenke GC,Neidhardt J,Owczarek-Lipska Mdoi
10.1002/mgg3.1388subject
Has Abstractpub_date
2020-09-01 00:00:00pages
e1388issue
9issn
2324-9269journal_volume
8pub_type
杂志文章abstract:BACKGROUND:The diagnostic workup in patients with a clinical suspicion of lysosomal storage diseases (LSD) is often difficult due to the variability in the clinical phenotype. The gold standard for diagnosis of LSDs consists of enzymatic testing. However, due to the sequential nature of this methodology and inconsisten...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.527
更新日期:2019-02-01 00:00:00
abstract::Galactose-1-phosphate uridylyltransferase (GALT) is a key enzyme in galactose metabolism, particularly important in the neonatal period due to ingestion of galactose-containing milk. GALT deficiency results in the genetic disorder classic galactosemia, whose pathophysiology is still not fully elucidated. Whereas class...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.94
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:To assess clinical chromosomal microarray (CMA) genomic testing reports for the following: (a) usage of reporting elements consistent with 2011 ACMG guidelines and other elements identified in the primary literature, (b) information quality, and (c) readability. METHODS:We retrospectively analyzed genomic test...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.551
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease-causing mutations can affect the BCKDHA, BCKDHB, and DBT genes encoding for the E1α, E1β, and E2 subunits of the multienzyme branched-chain α-keto acid dehydrogenase (BCKDH) complex. In the present study, nov...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1337
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Pre-mRNA splicing is a complex process requiring the identification of donor site, acceptor site, and branch point site with an adjacent polypyrimidine tract sequence. Splicing is regulated by splicing regulatory elements (SREs) with both enhancer and suppressor functions. Variants located in exonic regions ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.840
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:β-Globin gene cluster haplotypes associated with the Hb D-Los Angeles mutation have been reported in many different locations in different populations including Italy, Iran, Thailand, Belgium, Mexico, Holland, and Turkey. In this study, we have identified genetic relationships and formation periods between t...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.499
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM# 617140) syndrome is a rare, autosomal dominant genetic disorder caused by heterozygous variants in the SON gene (OMIM#182465, GenBank#NC_000021.9). There are only 33 cases and 26 causative SON variants reported to date since the first report in 2015. Here, we report a n...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1496
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highl...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1351
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Beta-propeller protein-associated neurodegeneration (BPAN, OMIM 300894) is an X-linked neurodegenerative disorder caused by mutations in WDR45. WDR45 is required for autophagy, defect in WDR45 impaired autophagy which contributes for the pathogenesis of BPAN. Previously, we reported a novel de novo mutation ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.858
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal tumor. However, the molecular mechanisms of KIRC pathogenesis remain little known. The purpose of our study was to identify potential key genes related to the occurrence and prognosis of KIRC, which could serve as novel diagnostic a...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.607
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:The Latrophilin 3 (LPHN3) gene (recently renamed Adhesion G protein-coupled receptor L3 (ADGRL3)) has been linked to susceptibility to attention deficit/hyperactivity disorder (ADHD) and vulnerability to addiction. However, its role and function are not well understood as there are no known functional varian...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.207
更新日期:2016-03-04 00:00:00
abstract:BACKGROUND:EAST syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to estab...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.227
更新日期:2016-06-07 00:00:00
abstract:BACKGROUND:Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease with colorectal adenomatous polyps as the main clinical manifestations. The objective of this study was to analyze and compare the expression levels of tumor proliferation and angiogenesis-related genes in different tissue secti...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1534
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Milroy-like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF-C variations found in a female proband b...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1389
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Retinoblastoma (Rb) is a rare intraocular malignant tumor in children with high overall survival. Predisposition to Rb is linked to RB1 germline mutations with high penetrance, but rare RB1 low-penetrance variants are also known. Rb survivors are at risk of second primary malignancies (SPMs), mostly osteosar...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.913
更新日期:2019-12-01 00:00:00
abstract:PURPOSE:Histone deacetylase inhibitor (HDACI) is a novel therapeutic option for cancer. However, the effects of HDACIs on chronic myeloid leukemia (CML) and the underlying mechanisms are still unknown. The aim of this study was to investigate the effect and the mechanism-of-action of two HDACI members, sodium butyrate ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.613
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:With the implementation of a research project providing whole genome sequencing (WGS) to all pediatric cancer patients in Denmark (2016-2019), we sought to investigate healthcare professionals' views on WGS as it was actively being implemented in pediatric oncology. METHODS:Semistructured interviews were ca...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1276
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Congenital disorder of glycosylation (CDG) type I is a group of rare disorders caused by recessive mutations in up to 25 genes that impair the N-glycan precursor formation and its transfer to proteins resulting in hypoglycosylation of multiple proteins. Congenital disorder of glycosylation causes multisystem...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1304
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Disordered inflammation and immune response is an acknowledged risk factor for cervical cancer development. Interleukin-1 receptor type 2 (IL1R2) is a decoy receptor for IL-1 cytokines and involved in host inflammatory and immune progression which could lead to the lesion and neoplasia of cervix. In this stu...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.516
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Due to the limited availability of mRNA analysis data, the number of exonic variants resulting in splicing impairment is underestimated although aberrant splicing correction is a promising therapeutic option to treat monogenic diseases, including choroideremia (CHM), a rare X-linked eye disorder arising from...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1490
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human m...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.724
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Genetic providers face the challenge of having adequate time to conduct a comprehensive evaluation. Hypermobile Ehlers-Danlos (hEDS) syndrome has a complex array of symptoms. An initial visit can involve approximately 60-80 min and an additional 45 min for the check-in and checkout process. We propose a mode...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.472
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Ankylosing spondylitis (AS) is the second most common cause of inflammatory arthritis worldwide affecting the axial skeleton. Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase-3 (MMP3) in the development of AS has few been investigated in Chinese population. METHODS:A total of 362 patients ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.752
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Tuberculosis (TB) is a significant worldwide health problem, and is caused by Mycobacteria tuberculosis. Recent studies have suggested that FOXO3 plays vital roles in the risk of immune-related infectious diseases such as TB. METHODS AND RESULTS:The present study aimed to evaluate FOXO3 genetic variants and...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.770
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Hearing loss (HL) is a common sensory disorder in humans characterized by extreme clinical and genetic heterogeneity. In recent years, next-generation sequencing (NGS) technologies have proven to be highly effective and powerful tools for population genetic studies of HL. Here, we analyzed clinical and molec...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1539
更新日期:2020-12-01 00:00:00
abstract:OBJECTIVES:This study aimed to investigate and confirm the association between 15 single nucleotide polymorphisms of four susceptibility genes (NBS1, TP53, PTEN, and BRIP1) and the susceptibility of breast cancer. METHODS:The genome DNA was extracted from peripheral blood and tumor tissues from one hundred and sevente...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1578
更新日期:2021-01-05 00:00:00
abstract:BACKGROUND:The ECE1 gene polymorphisms have been studied as a candidate gene in essential hypertension, but no consensus has been reached. To systematically explore their possible association, a case-control study was conducted. METHODS:This study included 398 hypertensive subjects and 596 healthy volunteers as contro...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1188
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Karyotype determination has a central role in the genetic workup of pregnancy loss, as aneuploidy (trisomy and monosomy) and polyploidy (triploidy and tetraploidy) are the cause in at least 50% of first trimester, 25% of second trimester, and 11% of third trimester miscarriages. There are several limitations...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.381
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:This study investigated the effects of haplotypes T-G and C-A derived from NG_012836.1:g.4160T>C and NG_012836.1:g.4326G>A on protein expression levels in vitro and identified the functional sequence in the regulatory region of the GABRB3 gene linked to possible associations with schizophrenia. METHODS:Reco...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.652
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Colon cancer is one of most malignant cancers around worldwide. Nearly 20% patients were diagnosed at colon cancer with metastasis. However, the lack of understanding regarding its pathogenesis brings difficulties to study it. METHODS:In this study, we acquired high-sequence data from GEO dataset, and perfo...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.588
更新日期:2019-04-01 00:00:00