Human Mutation

Cover image for Vol. 34 Issue 6

June 2013

Volume 34, Issue 6

Pages v–v, 801–925

  1. Features

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. You have free access to this content
    2. You have free access to this content
  2. Mutation Updates

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain (pages 801–811)

      Partha Sen, Yaping Yang, Colby Navarro, Iris Silva, Przemyslaw Szafranski, Katarzyna E. Kolodziejska, Avinash V. Dharmadhikari, Hasnaa Mostafa, Harry Kozakewich, Debra Kearney, John B. Cahill, Merrissa Whitt, Masha Bilic, Linda Margraf, Adrian Charles, Jack Goldblatt, Kathleen Gibson, Patrick E. Lantz, A. Julian Garvin, John Petty, Zeina Kiblawi, Craig Zuppan, Allyn McConkie-Rosell, Marie T. McDonald, Stacey L. Peterson-Carmichael, Jane T. Gaede, Binoy Shivanna, Deborah Schady, Philippe S. Friedlich, Stephen R. Hays, Irene Valenzuela Palafoll, Ulrike Siebers-Renelt, Axel Bohring, Laura S. Finn, Joseph R. Siebert, Csaba Galambos, Lananh Nguyen, Melissa Riley, Nicolas Chassaing, Adeline Vigouroux, Gustavo Rocha, Susana Fernandes, Jane Brumbaugh, Kari Roberts, Luk Ho-ming, Ivan F. M. Lo, Stephen Lam, Romana Gerychova, Marta Jezova, Iveta Valaskova, Florence Fellmann, Katayoun Afshar, Eric Giannoni, Vincent Muhlethaler, Jinlong Liang, Jacques S. Beckmann, Janet Lioy, Hitesh Deshmukh, Lakshmi Srinivasan, Daniel T. Swarr, Melissa Sloman, Charles Shaw-Smith, Rosa Laura van Loon, Cecilia Hagman, Yves Sznajer, Catherine Barrea, Christine Galant, Thierry Detaille, Jennifer A. Wambach, F. Sessions Cole, Aaron Hamvas, Lawrence S. Prince, Karin E.M. Diderich, Alice S. Brooks, Robert M. Verdijk, Hari Ravindranathan, Ella Sugo, David Mowat, Michael L. Baker, Claire Langston, Stephen Welty and Pawel Stankiewicz

      Article first published online: 12 APR 2013 | DOI: 10.1002/humu.22313

      Thumbnail image of graphical abstract

      FOXF1 mutations result in Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins, a deadly neonatal lung disorder that is uniformly fatal. The data in the article is the outcome of a global collaboration presenting the up to date list of causative mutations in FOXF1. The maternally inherited familial cases support the paternal imprinting of the gene in human lungs.

    2. TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update (pages 812–826)

      Serena Lattante, Guy A. Rouleau and Edor Kabashi

      Article first published online: 29 APR 2013 | DOI: 10.1002/humu.22319

      Thumbnail image of graphical abstract

      Amyotrophic Lateral Sclerosis is a progressive and devastating disorder of motor neurons. A number of genes have been found commonly mutated in ALS patients. Among these, TARDBP and FUS play an important role. Both proteins are involved in mRNA transport, axonal maintenance and motor neuron development but the exact molecular mechanisms through which they cause motor neuron degeneration, when mutated, are not well understood. This report summarizes the genetic, biological and clinical relevance of TARDBP and FUS mutations in ALS.

    3. DNA Variations in Oculocutaneous Albinism: An Updated Mutation List and Current Outstanding Issues in Molecular Diagnostics (pages 827–835)

      Dimitre R. Simeonov, Xinjing Wang, Chen Wang, Yuri Sergeev, Monika Dolinska, Matthew Bower, Roxanne Fischer, David Winer, Genia Dubrovsky, Joan Z. Balog, Marjan Huizing, Rachel Hart, Wadih M. Zein, William A. Gahl, Brian P. Brooks and David R. Adams

      Article first published online: 30 APR 2013 | DOI: 10.1002/humu.22315

      Thumbnail image of graphical abstract

      Isolated oculocutaneous albinism (OCA) is an autosomal recessive condition causing low vision and hypopigmentation. The article provides a mutation update for the OCA genes and discusses several challenging aspects of OCA molecular diagnostics, including the temperature sensitive TYR p.R402Q mutation, OCA-1 subtyping and the presence of a substantial minority of affected individuals with apparent missing heritability. A comprehensive list of previously reported mutations is provided as supplementary material, and includes collated ethnicity information, carrier frequencies, and in silico pathogenicity predictions.

  3. Informatics

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. You have free access to this content
      GEnomes Management Application (GEM.app): A New Software Tool for Large-Scale Collaborative Genome Analysis (pages 842–846)

      Michael A. Gonzalez, Rafael F. Acosta Lebrigio, Derek Van Booven, Rick H. Ulloa, Eric Powell, Fiorella Speziani, Mustafa Tekin, Rebecca Schüle and Stephan Züchner

      Article first published online: 3 APR 2013 | DOI: 10.1002/humu.22305

      Thumbnail image of graphical abstract

      The web-based tool Genomes Management Application is used in 15 different countries and provides easy to use yet powerful and fast analysis over hundreds of exomes.

    2. Simple Detection of Germline Microsatellite Instability for Diagnosis of Constitutional Mismatch Repair Cancer Syndrome (pages 847–852)

      Danielle Ingham, Christine P. Diggle, Ian Berry, Claire A. Bristow, Bruce E. Hayward, Nazneen Rahman, Alexander F. Markham, Eamonn G. Sheridan, David T. Bonthron and Ian M. Carr

      Article first published online: 2 APR 2013 | DOI: 10.1002/humu.22311

      Thumbnail image of graphical abstract

      Mutations in the DNA mismatch repair genes predispose to childhood cancers. However, detection of constitutional or germline MSI (gMSI) has hitherto relied on technically difficult assays that are not routinely applicable for clinical diagnosis. Consequently, we have developed a simple high throughput screening methodology to detect gMSI in CMMRD patients based on the presence of stutter peaks flanking a dinucleotide repeat allele when amplified from patient blood DNA samples.

    3. Prioritization of Retinal Disease Genes: An Integrative Approach (pages 853–859)

      Alex H. Wagner, Kyle R. Taylor, Adam P. DeLuca, Thomas L. Casavant, Robert F. Mullins, Edwin M. Stone, Todd E. Scheetz and Terry A. Braun

      Article first published online: 12 APR 2013 | DOI: 10.1002/humu.22317

      Thumbnail image of graphical abstract

      Using a diverse set of publicly available experiments, we construct a model that identifies patterns among known retinal disease causing genes. We use this model to prioritize variants identified in exome studies of patients diagnosed with Retinitis Pigmentosa (RP). We show that our model significantly enriches RP variant candidate lists and outperforms state-of-the-art methods in generalized gene prediction strategies.

  4. Brief Reports

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. You have free access to this content
      Do Not Trust the Pedigree: Reduced and Sex-Dependent Penetrance at a Novel Mutation Hotspot in ATL1 Blurs Autosomal Dominant Inheritance of Spastic Paraplegia (pages 860–863)

      Rita-Eva Varga, Rebecca Schüle, Hicham Fadel, Irene Valenzuela, Fiorella Speziani, Michael Gonzalez, Galina Rudenskaia, Gudrun Nürnberg, Holger Thiele, Janine Altmüller, Victoria Alvarez, Josep Gamez, James Y. Garbern, Peter Nürnberg, Stephan Zuchner and Christian Beetz

      Article first published online: 5 APR 2013 | DOI: 10.1002/humu.22309

      Thumbnail image of graphical abstract

      Inheritance patterns usually guide gene selection in mutational screening strategies. By whole exome sequencing of index cases with apparently novel forms of spastic paraplegia, we identify a mutational hotspot in the known dominant gene ATL1 and show that corresponding alterations are associated with a highly reduced and partially sex-dependent risk of developing the disease. Our findings suggest that misleading family history may contribute to missing heritability in genetically heterogeneous disorders.

    2. You have full text access to this OnlineOpen article
      Deficiency of the Cyclin-Dependent Kinase Inhibitor, CDKN1B, Results in Overgrowth and Neurodevelopmental Delay (pages 864–868)

      William Grey, Louise Izatt, Wafa Sahraoui, Yiu-Ming Ng, Caroline Ogilvie, Anthony Hulse, Eric Tse, Roman Holic and Veronica Yu

      Article first published online: 12 APR 2013 | DOI: 10.1002/humu.22314

      Thumbnail image of graphical abstract

      Recessive threshold model of CDKN1B in neurodevelopment. Model depicting the proband case with maternally deleted CDKN1B and a de novo variant c.-73G>A on the paternal allele. This leads to an overall decrease in CDKN1B protein level, impacting on neurodevelopment.

    3. Novel Compound Heterozygous Mutations in TBC1D24 Cause Familial Malignant Migrating Partial Seizures of Infancy (pages 869–872)

      Mathieu Milh, Antonio Falace, Nathalie Villeneuve, Nicola Vanni, Pierre Cacciagli, Stefania Assereto, Rima Nabbout, Fabio Benfenati, Federico Zara, Brigitte Chabrol, Laurent Villard and Anna Fassio

      Article first published online: 12 APR 2013 | DOI: 10.1002/humu.22318

      Thumbnail image of graphical abstract

      We identified novel inherited mutations in TBC1D24 in two siblings affected by Malignant Migrating Partial Seizures of Infancy (MMPSI), a rare devastating early onset epileptic encephalopaties of heterogeneous genetic origin. TBC1D24 is a novel epilepsy gene encoding a neuronal protein known to interact with ARF6 and to regulate neurite development. The pathogenic TBC1D24 variants are located in the ARF6 binding domain and severely impaired TBC1D24 expression and function.

  5. Research Articles

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. Combined Computational–Experimental Analyses of CFTR Exon Strength Uncover Predictability of Exon-Skipping Level (pages 873–881)

      Abdel Aissat, Alix de Becdelièvre, Lisa Golmard, Christian Vasseur, Catherine Costa, Asma Chaoui, Natacha Martin, Bruno Costes, Michel Goossens, Emmanuelle Girodon, Pascale Fanen and Alexandre Hinzpeter

      Article first published online: 28 MAR 2013 | DOI: 10.1002/humu.22300

      Thumbnail image of graphical abstract

      Using fourteen different freely available in silico tools, we identified some exons in the CFTR gene presenting weaker splicing motifs than other exons. These exons exhibit higher rates of basal skipping as determined by minigene assays and are more likely to contain exon-skipping substitutions. Our approach, which identifies exons with some splicing signal weaknesses, will help researchers to find splicing mutations of clinical relevance.

    2. Transition to Next Generation Analysis of the Whole Mitochondrial Genome: A Summary of Molecular Defects (pages 882–893)

      Sha Tang, Jing Wang, Victor Wei Zhang, Fang-Yuan Li, Megan Landsverk, Hong Cui, Cavatina K. Truong, Guoli Wang, Li Chieh Chen, Brett Graham, Fernando Scaglia, Eric S. Schmitt, William J. Craigen and Lee-Jun C. Wong

      Article first published online: 2 APR 2013 | DOI: 10.1002/humu.22307

      Thumbnail image of graphical abstract

      This article summarizes the results of mitochondrial DNA (mtDNA) mutation analysis of a large cohort of patients with suspected mitochondrial disease using three different approaches — screening for common mtDNA point mutations and large deletions, sequencing the entire mtDNA by Sanger sequencing, and mtDNA mutation analyses employing Next-Generation sequencing (mtWGS-NGS). We demonstrate that the comprehensive mtWGS-NGS methodology can simultaneously detect mtDNA point mutations with high sensitivity, accurately quantify mutation heteroplasmy, and detect large mtDNA deletions with breakpoints precisely mapped.

    3. EEC- and ADULT-Associated TP63 Mutations Exhibit Functional Heterogeneity Toward P63 Responsive Sequences (pages 894–904)

      Paola Monti, Debora Russo, Renata Bocciardi, Giorgia Foggetti, Paola Menichini, Maria T. Divizia, Margherita Lerone, Claudio Graziano, Anita Wischmeijer, Hector Viadiu, Roberto Ravazzolo, Alberto Inga and Gilberto Fronza

      Article first published online: 2 APR 2013 | DOI: 10.1002/humu.22304

      Thumbnail image of graphical abstract

      Germline TP63 mutations are responsible for a group of human ectodermal dysplasia syndromes. Different TP63 alleles identified in ADULT and EEC patients were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA-binding domain. Interestingly, the mutants associated with the ADULT phenotype were characterized by a severe defect in transactivation on DN-P63α-specific response elements derived from genes closely related to the clinical manifestations of the TP63-associated syndromes, namely PERP and COL18A1.

    4. The Spectrum of ELANE Mutations and their Implications in Severe Congenital and Cyclic Neutropenia (pages 905–914)

      Manuela Germeshausen, Sabine Deerberg, Yvonne Peter, Christina Reimer, Christian P. Kratz and Matthias Ballmaier

      Article first published online: 2 APR 2013 | DOI: 10.1002/humu.22308

      Thumbnail image of graphical abstract

      We analyzed the spectrum of ELANE mutations, which are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN). Using predictive algorithms we found a trend for a more benign prediction of CyN-associated mutations compared to those associated with CN. Within the group of CN the course of disease was more severe in patients with ELANE mutation compared to patients without ELANE mutations. The predictive value of specific ELANE mutations for leukemogenesis was low.

  6. Meeting Reports

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. You have free access to this content
      Towards a Universal Clinical Genomics Database: The 2012 International Standards for Cytogenomic Arrays Consortium Meeting (pages 915–919)

      Erin Rooney Riggs, Karen E. Wain, Darlene Riethmaier, Melissa Savage, Bethanny Smith-Packard, Erin B. Kaminsky, Heidi L. Rehm, Christa Lese Martin, David H. Ledbetter and W. Andrew Faucett

      Article first published online: 2 APR 2013 | DOI: 10.1002/humu.22306

      Thumbnail image of graphical abstract

      The 2012 International Standards for Cytogenomic Arrays (ISCA) Consortium Meeting was held in Bethesda, Maryland, May 21-22, 2012. The program centered on expanding the current focus of the Consortium to include the collection and curation of structural and sequence-level variation into a unified clinical genomics database, available to the public through resources such as the ClinVar database. Here, we announce plans to change our name to the International Collaboration for Clinical Genomics (ICCG) to reflect our expanded efforts.

  7. Letters to the Editor

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. You have free access to this content
    2. You have free access to this content
      Response to: Design of a Core Classification Process for DNA Mismatch Repair Variations of A Priori Unknown Functional Significance (pages 923–924)

      Lene Juel Rasmussen, Christopher D. Heinen, Brigitte Royer-Pokora, Mark Drost, Sean Tavtigian, Robert M.W. Hofstra and Niels de Wind

      Article first published online: 28 MAR 2013 | DOI: 10.1002/humu.22310

  8. Erratum

    1. Top of page
    2. Features
    3. Mutation Updates
    4. Informatics
    5. Brief Reports
    6. Research Articles
    7. Meeting Reports
    8. Letters to the Editor
    9. Erratum
    1. You have free access to this content
      RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs (page 925)

      Radhakrishnan Sabarinathan, Hakim Tafer, Stefan E. Seemann, Ivo L. Hofacker, Peter F. Stadler and Jan Gorodkin

      Article first published online: 9 APR 2013 | DOI: 10.1002/humu.22323

      This article corrects:

      RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs

      Vol. 34, Issue 4, 546–556, Article first published online: 20 MAR 2013

SEARCH

SEARCH BY CITATION