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  1. Article ; Online: Trichothiodystrophy-associated MPLKIP maintains DBR1 levels for proper lariat debranching and ectodermal differentiation.

    Theil, Arjan F / Pines, Alex / Kalayci, Tuğba / Heredia-Genestar, José M / Raams, Anja / Rietveld, Marion H / Sridharan, Sriram / Tanis, Sabine Ej / Mulder, Klaas W / Büyükbabani, Nesimi / Karaman, Birsen / Uyguner, Zehra O / Kayserili, Hülya / Hoeijmakers, Jan Hj / Lans, Hannes / Demmers, Jeroen Aa / Pothof, Joris / Altunoglu, Umut / El Ghalbzouri, Abdoelwaheb /
    Vermeulen, Wim

    EMBO molecular medicine

    2023  Volume 15, Issue 11, Page(s) e17973

    Abstract: The brittle hair syndrome Trichothiodystrophy (TTD) is characterized by variable clinical features, including photosensitivity, ichthyosis, growth retardation, microcephaly, intellectual disability, hypogonadism, and anaemia. TTD-associated mutations ... ...

    Abstract The brittle hair syndrome Trichothiodystrophy (TTD) is characterized by variable clinical features, including photosensitivity, ichthyosis, growth retardation, microcephaly, intellectual disability, hypogonadism, and anaemia. TTD-associated mutations typically cause unstable mutant proteins involved in various steps of gene expression, severely reducing steady-state mutant protein levels. However, to date, no such link to instability of gene-expression factors for TTD-associated mutations in MPLKIP/TTDN1 has been established. Here, we present seven additional TTD individuals with MPLKIP mutations from five consanguineous families, with a newly identified MPLKIP variant in one family. By mass spectrometry-based interaction proteomics, we demonstrate that MPLKIP interacts with core splicing factors and the lariat debranching protein DBR1. MPLKIP-deficient primary fibroblasts have reduced steady-state DBR1 protein levels. Using Human Skin Equivalents (HSEs), we observed impaired keratinocyte differentiation associated with compromised splicing and eventually, an imbalanced proteome affecting skin development and, interestingly, also the immune system. Our data show that MPLKIP, through its DBR1 stabilizing role, is implicated in mRNA splicing, which is of particular importance in highly differentiated tissue.
    MeSH term(s) Humans ; Adaptor Proteins, Signal Transducing/metabolism ; Consanguinity ; Mutation ; Phenotype ; RNA Splicing ; Trichothiodystrophy Syndromes/genetics ; Trichothiodystrophy Syndromes/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; MPLKIP protein, human ; Dbr1 protein, human (EC 2.7.7.-)
    Language English
    Publishing date 2023-10-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202317973
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6784: Show issues Location:
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  2. Article ; Online: Turkish Ectodermal Dysplasia Cohort: From Phenotype to Genotype in 17 Families.

    Güven, Yeliz / Bal, Elodie / Altunoglu, Umut / Yücel, Esra / Hadj-Rabia, Smail / Koruyucu, Mine / Bahar Tuna, Elif / Çıldır, Şule / Aktören, Oya / Bodemer, Christine / Uyguner, Zehra O / Smahi, Asma / Kayserili, Hülya

    Cytogenetic and genome research

    2019  Volume 157, Issue 4, Page(s) 189–196

    Abstract: Hypohidrotic or anhidrotic ectodermal dysplasia (HED/EDA) is characterized by impaired development of the hair, teeth, or sweat glands. HED/EDA is inherited in an X-linked, autosomal dominant, or autosomal recessive pattern and caused by the pathogenic ... ...

    Abstract Hypohidrotic or anhidrotic ectodermal dysplasia (HED/EDA) is characterized by impaired development of the hair, teeth, or sweat glands. HED/EDA is inherited in an X-linked, autosomal dominant, or autosomal recessive pattern and caused by the pathogenic variants in 4 genes: EDA, EDAR, EDARADD, and WNT10A. The aim of the present study was to perform molecular screening of these 4 genes in a cohort of Turkish individuals diagnosed with HED/EDA. We screened for pathogenic variants of WNT10A, EDA, EDAR, and EDARADD through Sanger sequencing. We further assessed the clinical profiles of the affected individuals in order to establish phenotype-genotype correlation. In 17 (63%) out of 27 families, 17 pathogenic variants, 8 being novel, were detected in the 4 well-known ectodermal dysplasia genes. EDAR and EDA variants were identified in 6 families each, WNT10A variants in 4, and an EDARADD variant in 1, accounting for 35.3, 35.3, 23.5, and 5.9% of mutation-positive families, respectively. The low mutation detection rate of the cohort and the number of the EDAR pathogenic variants being as high as the EDA ones were the most noteworthy findings which could be attributed to the high consanguinity rate.
    MeSH term(s) Consanguinity ; Ectodermal Dysplasia/genetics ; Ectodysplasins/genetics ; Edar Receptor/genetics ; Edar-Associated Death Domain Protein/genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Sequence Analysis, DNA/methods ; Turkey ; Wnt Proteins/genetics
    Chemical Substances EDA protein, human ; EDAR protein, human ; EDARADD protein, human ; Ectodysplasins ; Edar Receptor ; Edar-Associated Death Domain Protein ; WNT10A protein, human ; Wnt Proteins
    Language English
    Publishing date 2019-04-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2087824-2
    ISSN 1424-859X ; 1424-8581
    ISSN (online) 1424-859X
    ISSN 1424-8581
    DOI 10.1159/000499325
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 512: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Clinical and Molecular Characterization of Fanconi Anemia Patients in Turkey.

    Toksoy, Güven / Uludağ Alkaya, Dilek / Bagirova, Gülendam / Avcı, Şahin / Aghayev, Agharza / Günes, Nilay / Altunoğlu, Umut / Alanay, Yasemin / Başaran, Seher / Berkay, Ezgi G / Karaman, Birsen / Celkan, Tiraje T / Apak, Hilmi / Kayserili, Hülya / Tüysüz, Beyhan / Uyguner, Zehra O

    Molecular syndromology

    2020  Volume 11, Issue 4, Page(s) 183–196

    Abstract: Fanconi anemia (FA) is a rare multigenic chromosomal instability syndrome that predisposes patients to life-threatening bone marrow failure, congenital malformations, and cancer. Functional loss of interstrand cross-link (ICL) DNA repair system is held ... ...

    Abstract Fanconi anemia (FA) is a rare multigenic chromosomal instability syndrome that predisposes patients to life-threatening bone marrow failure, congenital malformations, and cancer. Functional loss of interstrand cross-link (ICL) DNA repair system is held responsible, though the mechanism is not yet fully understood. The clinical and molecular findings of 20 distinct FA cases, ages ranging from perinatal stage to 32 years, are presented here. Pathogenic variants in
    Language English
    Publishing date 2020-09-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2546218-0
    ISSN 1661-8777 ; 1661-8769
    ISSN (online) 1661-8777
    ISSN 1661-8769
    DOI 10.1159/000509838
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis.

    Dinckan, Nuriye / Du, Renqian / Akdemir, Zeynep C / Bayram, Yavuz / Jhangiani, Shalini N / Doddapaneni, Harsha / Hu, Jianhong / Muzny, Donna M / Guven, Yeliz / Aktoren, Oya / Kayserili, Hulya / Boerwinkle, Eric / Gibbs, Richard A / Posey, Jennifer E / Lupski, James R / Uyguner, Zehra O / Letra, Ariadne

    American journal of medical genetics. Part A

    2018  Volume 176, Issue 4, Page(s) 1015–1022

    Abstract: Tooth development is regulated by multiple genetic pathways, which ultimately drive the complex interactions between the oral epithelium and mesenchyme. Disruptions at any time point during this process may lead to failure of tooth development, also ... ...

    Abstract Tooth development is regulated by multiple genetic pathways, which ultimately drive the complex interactions between the oral epithelium and mesenchyme. Disruptions at any time point during this process may lead to failure of tooth development, also known as tooth agenesis (TA). TA is a common craniofacial abnormality in humans and represents the failure to develop one or more permanent teeth. Many genes and potentially subtle variants in these genes contribute to the TA phenotype. We report the clinical and genetic impact of a rare homozygous ANTXR1 variant (c.1312C>T), identified by whole exome sequencing (WES), in a consanguineous Turkish family with TA. Mutations in ANTXR1 have been associated with GAPO (growth retardation, alopecia, pseudoanodontia, and optic atrophy) syndrome and infantile hemangioma, however no clinical characteristics associated with these conditions were observed in our study family. We detected the expression of Antxr1 in oral and dental tissues of developing mouse embryos, further supporting a role for this gene in tooth development. Our findings implicate ANTXR1 as a candidate gene for isolated TA, suggest the involvement of specific hypomorphic alleles, and expand the previously known ANTXR1-associated phenotypes.
    MeSH term(s) Alleles ; Amino Acid Substitution ; Animals ; Anodontia/diagnosis ; Anodontia/genetics ; Child ; Consanguinity ; Facies ; Genetic Association Studies ; Genotype ; Humans ; Male ; Mice ; Microfilament Proteins ; Mutation ; Neoplasm Proteins/genetics ; Pedigree ; Phenotype ; Radiography ; Receptors, Cell Surface/genetics ; Exome Sequencing
    Chemical Substances ANTXR1 protein, human ; Microfilament Proteins ; Neoplasm Proteins ; Receptors, Cell Surface
    Language English
    Publishing date 2018-02-13
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.38625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1376/A: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article: Turkish Ectodermal Dysplasia Cohort: From Phenotype to Genotype in 17 Families

    Güven, Yeliz / Bal, Elodie / Altunoglu, Umut / Yücel, Esra / Hadj-Rabia, Smail / Koruyucu, Mine / Bahar Tuna, Elif / Çıldır, Şule / Aktören, Oya / Bodemer, Christine / Uyguner, Zehra O. / Smahi, Asma / Kayserili, Hülya

    Cytogenetic and Genome Research

    2019  Volume 157, Issue 4, Page(s) 189–196

    Abstract: Hypohidrotic or anhidrotic ectodermal dysplasia (HED/EDA) is characterized by impaired development of the hair, teeth, or sweat glands. HED/EDA is inherited in an X-linked, autosomal dominant, or autosomal recessive pattern and caused by the pathogenic ... ...

    Institution Department of Pedodontics, Faculty of Dentistry, and Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University Pedodontics Unit, Dentway Dental Care, and Department of Medical Genetics, Koç University School of Medicine (KUSoM), Istanbul, Turkey Université Paris Descartes - Sorbonne Paris Cité, INSERM U1163, Institut Imagine, Hôpital Universitaire Necker-Enfants Malades, and Department of Dermatology and Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), Paris, France
    Abstract Hypohidrotic or anhidrotic ectodermal dysplasia (HED/EDA) is characterized by impaired development of the hair, teeth, or sweat glands. HED/EDA is inherited in an X-linked, autosomal dominant, or autosomal recessive pattern and caused by the pathogenic variants in 4 genes: EDAEDAREDARADD, and WNT10A. The aim of the present study was to perform molecular screening of these 4 genes in a cohort of Turkish individuals diagnosed with HED/EDA. We screened for pathogenic variants of WNT10AEDAEDAR, and EDARADD through Sanger sequencing. We further assessed the clinical profiles of the affected individuals in order to establish phenotype-genotype correlation. In 17 (63%) out of 27 families, 17 pathogenic variants, 8 being novel, were detected in the 4 well-known ectodermal dysplasia genes. EDAR and EDA variants were identified in 6 families each, WNT10A variants in 4, and an EDARADD variant in 1, accounting for 35.3, 35.3, 23.5, and 5.9% of mutation-positive families, respectively. The low mutation detection rate of the cohort and the number of the EDAR pathogenic variants being as high as the EDA ones were the most noteworthy findings which could be attributed to the high consanguinity rate.
    Keywords Ectodermal dysplasia
    Language English
    Publishing date 2019-04-12
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Original Article
    ZDB-ID 2087824-2
    ISSN 1424-859X ; 1424-8581
    ISSN (online) 1424-859X
    ISSN 1424-8581
    DOI 10.1159/000499325
    Database Karger publisher's database

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 512: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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