Human Mutation

Cover image for Vol. 38 Issue 2

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Garry R. Cutting

Impact Factor: 5.089

ISI Journal Citation Reports © Ranking: 2015: 23/166 (Genetics & Heredity)

Online ISSN: 1098-1004


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  1. Methods

    1. Detecting AGG Interruptions in Male and Female FMR1 Premutation Carriers by Single-Molecule Sequencing

      Simon Ardui, Valerie Race, Alena Zablotskaya, Matthew S. Hestand, Hilde Van Esch, Koenraad Devriendt, Gert Matthijs and Joris R. Vermeesch

      Version of Record online: 17 JAN 2017 | DOI: 10.1002/humu.23150

      Thumbnail image of graphical abstract

      Single-Molecule Sequencing enables the detection of AGG units interrupting the CGG repeat of the FMRl gene not only in males, but also in females. This knowledge is of great value to determine the risk a female with an FMRl premutation (55–200 repeat units) will transmit a full mutation (>200 repeat units) to her offspring.

  2. Brief Reports

    1. Doublet-Mediated DNA Rearrangement—A Novel and Potentially Underestimated Mechanism for the Formation of Recurrent Pathogenic Deletions

      Amir Jahic, Sophie Hinreiner, Werner Emberger, Ute Hehr, Stephan Zuchner and Christian Beetz

      Version of Record online: 13 JAN 2017 | DOI: 10.1002/humu.23162

      Thumbnail image of graphical abstract

      Doublets are small local copies of unique sequence. (A) We identified pathogenic deletions which are apparently mediated by homology (grey bars) between pre-existing doublets. (B) Hypothetical two-step event consisting of doublet generation and subsequent doublet-mediated deletion. The resulting sequence would be misinterpreted as resulting from a non-homology-based one-step mechanism such as non-homologous end-joining (grey lines).

  3. Informatics

    1. You have full text access to this OnlineOpen article
      The Clinical Next-Generation Sequencing Database: A Tool for the Unified Management of Clinical Information and Genetic Variants to Accelerate Variant Pathogenicity Classification

      Shin-ya Nishio and Shin-ichi Usami

      Version of Record online: 11 JAN 2017 | DOI: 10.1002/humu.23160

      Thumbnail image of graphical abstract

      In this report, we describe an original database development tool, named the “Clinical Next Generation Sequencing Database”, which can be utilized for efficient clinical NGS analysis of inherited diseases through the collection of data for a large number of variants as well as clinical information in a unified interface.

      This database was also intended to assist in efficient variant pathogenicity interpretation by gathering all knowledge about the variant and comparing the clinical features of each patient.

  4. Brief Reports

    1. Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry

      Tuomas Heikkinen, Kati Kämpjärvi, Salla Keskitalo, Pernilla von Nandelstadh, Xiaonan Liu, Ville Rantanen, Esa Pitkänen, Matias Kinnunen, Heikki Kuusanmäki, Mika Kontro, Mikko Turunen, Netta Mäkinen, Jussi Taipale, Caroline Heckman, Kaisa Lehti, Satu Mustjoki, Markku Varjosalo and Pia Vahteristo

      Version of Record online: 11 JAN 2017 | DOI: 10.1002/humu.23157

      Thumbnail image of graphical abstract

      We analyzed the functions of a MED12 5′ end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and showed that the mutation escapes nonsense mediated mRNA decay (NMD) by using an alternative translation initiation site. The inability of the N-terminally truncated mutant protein to enter the nucleus abolished all interactions between MED12 and the Mediator complex components and led to the identification of a nuclear localization signal (NLS) in the MED12 protein.

  5. Research Articles

    1. Landscape of Pleiotropic Proteins Causing Human Disease: Structural and System Biology Insights

      Sirawit Ittisoponpisan, Eman Alhuzimi, Michael J. E. Sternberg and Alessia David

      Version of Record online: 11 JAN 2017 | DOI: 10.1002/humu.23155

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      Pleiotropic proteins are important contributors to rare and common disorders. In this study, we demonstrate that this class of proteins is biologically different compared to non-pleiotropic proteins. We show that pleiotropic proteins are enriched in deleterious and rare variants, but not common variants. They are also more likely to be involved in the pathogenesis of neoplasias, neurological and circulatory diseases, and congenital malformations compared to non-pleiotropic proteins, which are more likely to be involved in endocrine and metabolic disorders.

  6. Brief Reports

    1. Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan–Herndon–Dudley Syndrome

      Francesca Novara, Stefan Groeneweg, Elena Freri, Margherita Estienne, Paolo Reho, Sara Matricardi, Barbara Castellotti, W. Edward Visser, Orsetta Zuffardi and Theo J. Visser

      Version of Record online: 5 JAN 2017 | DOI: 10.1002/humu.23140

      Thumbnail image of graphical abstract

      Mutations in the thyroid hormone transporter SLC16A2 (MCT8) result in the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe intellectual disability and abnormal serum thyroid hormone levels. Here, we report 3 newly identified AHDS patients, of whom 2 carry a different mutation affecting the same Gly564 residue (p.G564E and p.G564R). Interestingly, a striking difference in severity of the clinical phenotype was observed between these 2 patients, which corresponded to the residual transporter activity of both mutant transporters in our in vitro studies.

  7. Research Articles

    1. SLC4A11 Three-Dimensional Homology Model Rationalizes Corneal Dystrophy-Causing Mutations

      Katherine E. Badior, Kumari Alka and Joseph R. Casey

      Version of Record online: 27 DEC 2016 | DOI: 10.1002/humu.23152

      Thumbnail image of graphical abstract

      SLC4A11 is a membrane transport protein whose mutations cause blinding corneal dystrophies. A homology model of the SLC4A11 integral membrane domain, developed on the basis of AE1 (SLC4A1), provided a means to understand the molecular basis for 37 different SLC4A11 corneal dystrophy mutations. Mutations fell broadly into four classes.


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