دورية أكاديمية
أعرض في EDS

Rare Noncoding Mutations Extend the Mutational Spectrum in the PGAP3 Subtype of Hyperphosphatasia with Mental Retardation Syndrome.

التفاصيل البيبلوغرافية
العنوان: Rare Noncoding Mutations Extend the Mutational Spectrum in the PGAP3 Subtype of Hyperphosphatasia with Mental Retardation Syndrome.
المؤلفون: Knaus A; Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany.; Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, Berlin, 14195, Germany.; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Campus Virchow Klinikum, Augustenburger Platz 1, Berlin, 13353, Germany., Awaya T; Department of Pediatrics, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, 6068507, Japan., Helbig I; Division of Child Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104-4399.; Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel 24105, Germany., Afawi Z; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Pendziwiat M; Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel 24105, Germany., Abu-Rachma J; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Thompson MD; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Cole DE; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Skinner S; Greenwood Genetic Center, Greenwood, South Carolina., Annese F; Greenwood Genetic Center, Greenwood, South Carolina., Canham N; North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow, HA1 3UJ, UK., Schweiger MR; Epigenomics and Tumor Genetics, CCG, University of Cologne, Cologne, 50931, Germany., Robinson PN; Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany.; Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, Berlin, 14195, Germany., Mundlos S; Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany.; Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, Berlin, 14195, Germany., Kinoshita T; Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, 565, Japan.; World Premier International Immunology Frontier Research Center, Osaka University, Osaka, 565, Japan., Munnich A; Hôpital Necker - Enfants Malades, Unité INSERM 781, Laboratoire de génétique moléculaire Tour Lavoisier - 2ème étage, Paris Cedex, 15 75743, France., Murakami Y; Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, 565, Japan.; World Premier International Immunology Frontier Research Center, Osaka University, Osaka, 565, Japan., Horn D; Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany., Krawitz PM; Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany.; Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, Berlin, 14195, Germany.
المصدر: Human mutation [Hum Mutat] 2016 Aug; Vol. 37 (8), pp. 737-44. Date of Electronic Publication: 2016 May 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 9215429 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-1004 (Electronic) Linking ISSN: 10597794 NLM ISO Abbreviation: Hum Mutat Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Wiley-Liss, c1992-
مواضيع طبية MeSH: Mutation, Missense* , Polymorphism, Single Nucleotide*, Abnormalities, Multiple/*genetics , Abnormalities, Multiple/*pathology , Intellectual Disability/*genetics , Intellectual Disability/*pathology , Phosphorus Metabolism Disorders/*genetics , Phosphorus Metabolism Disorders/*pathology , RNA, Messenger/*genetics , Receptors, Cell Surface/*genetics, 3' Untranslated Regions ; Adolescent ; Adult ; Carboxylic Ester Hydrolases ; Cells, Cultured ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Humans ; Introns ; Male ; Pedigree ; Sequence Analysis, DNA/methods ; Young Adult
مستخلص: HPMRS or Mabry syndrome is a heterogeneous glycosylphosphatidylinositol (GPI) anchor deficiency that is caused by an impairment of synthesis or maturation of the GPI-anchor. The expressivity of the clinical features in HPMRS varies from severe syndromic forms with multiple organ malformations to mild nonsyndromic intellectual disability. In about half of the patients with the clinical diagnosis of HPMRS, pathogenic mutations can be identified in the coding region in one of the six genes, one among them is PGAP3. In this work, we describe a screening approach with sequence specific baits for transcripts of genes of the GPI pathway that allows the detection of functionally relevant mutations also including introns and the 5' and 3' UTR. By this means, we also identified pathogenic noncoding mutations, which increases the diagnostic yield for HPMRS on the basis of intellectual disability and elevated serum alkaline phosphatase. In eight affected individuals from different ethnicities, we found seven novel pathogenic mutations in PGAP3. Besides five missense mutations, we identified an intronic mutation, c.558-10G>A, that causes an aberrant splice product and a mutation in the 3'UTR, c.*559C>T, that is associated with substantially lower mRNA levels. We show that our novel screening approach is a useful rapid detection tool for alterations in genes coding for key components of the GPI pathway.
(© 2016 The Authors. **Human Mutation published by Wiley Periodicals, Inc.)
References: Am J Hum Genet. 2012 Jul 13;91(1):146-51. (PMID: 22683086)
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7400-5. (PMID: 9207103)
J Biochem. 2008 Sep;144(3):287-94. (PMID: 18635593)
Am J Hum Genet. 2013 Apr 4;92(4):584-9. (PMID: 23561847)
Mol Biol Cell. 2007 Apr;18(4):1497-506. (PMID: 17314402)
J Pediatr. 1970 Jul;77(1):74-85. (PMID: 5465362)
Am J Med Genet A. 2011 Aug;155A(8):1917-22. (PMID: 21739589)
Epilepsia. 2014 Feb;55(2):e13-7. (PMID: 24417746)
Biol Direct. 2011 Jul 06;6:37. (PMID: 21733186)
Hum Mol Genet. 2015 Nov 1;24(21):6146-59. (PMID: 26293662)
Eur J Med Genet. 2010 Mar-Apr;53(2):85-8. (PMID: 20080219)
Am J Hum Genet. 2014 Feb 6;94(2):161-75. (PMID: 24507773)
Lab Invest. 1999 Mar;79(3):293-9. (PMID: 10092065)
Am J Med Genet A. 2010 Jul;152A(7):1661-9. (PMID: 20578257)
Nat Med. 2006 Jul;12(7):846-51. (PMID: 16767100)
Am J Hum Genet. 2013 Apr 4;92(4):575-83. (PMID: 23561846)
J Med Genet. 2014 Mar;51(3):203-7. (PMID: 24367057)
Am J Hum Genet. 2014 Feb 6;94(2):278-87. (PMID: 24439110)
Nat Genet. 2010 Oct;42(10):827-9. (PMID: 20802478)
فهرسة مساهمة: Keywords: Mabry syndrome; PGAP3; hyperphosphatasia with mental retardation; intellectual disability; noncoding mutations
المشرفين على المادة: 0 (3' Untranslated Regions)
0 (RNA, Messenger)
0 (Receptors, Cell Surface)
EC 3.1.1.- (Carboxylic Ester Hydrolases)
EC 3.1.1.- (PGAP3 protein, human)
SCR Disease Name: Hyperphosphatasia with Mental Retardation
تواريخ الأحداث: Date Created: 20160428 Date Completed: 20171215 Latest Revision: 20201209
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC5084765
DOI: 10.1002/humu.23006
PMID: 27120253
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-1004
DOI:10.1002/humu.23006