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Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation

Ashikov, Angel
Author Ashikov, Angel Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Abu Bakar, Nurulamin
Author Abu Bakar, Nurulamin Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Wen, Xiao-Yan
Author Wen, Xiao-Yan Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada Department of Medicine, Physiology & Institute of Medical Science, Faculty of Medicine, University of Toronto, ON, Canada
Niemeijer, Marco
Author Niemeijer, Marco Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Rodrigues Pinto Osorio, Glentino
Author Rodrigues Pinto Osorio, Glentino Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Brand-Arzamendi, Koroboshka
Author Brand-Arzamendi, Koroboshka Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada Department of Medicine, Physiology & Institute of Medical Science, Faculty of Medicine, University of Toronto, ON, Canada
Hasadsri, Linda
Author Hasadsri, Linda Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Hansikova, Hana
Author Hansikova, Hana Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Raymond, Kimiyo
Author Raymond, Kimiyo Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Vicogne, Dorothée
Author Vicogne, Dorothée CNRS-UMR 8576, Structural and Functional Glycobiology Unit, FRABIO, University of Lille, 59655 Villeneuve d'Ascq, France
Ondruskova, Nina
Author Ondruskova, Nina Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Simon, Marleen E H
Author Simon, Marleen E H Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Pfundt, Rolph
Author Pfundt, Rolph Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Timal, Sharita
Author Timal, Sharita Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Beumers, Roel
Author Beumers, Roel Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Biot, Christophe
Author Biot, Christophe CNRS-UMR 8576, Structural and Functional Glycobiology Unit, FRABIO, University of Lille, 59655 Villeneuve d'Ascq, France
Smeets, Roel
Author Smeets, Roel Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Kersten, Marjan
Author Kersten, Marjan Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Huijben, Karin
Author Huijben, Karin Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
CDG group
Author CDG group
Linders, Peter T A
Author Linders, Peter T A Department of Tumor Immunology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
van den Bogaart, Geert
Author van den Bogaart, Geert Department of Tumor Immunology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
van Hijum, Sacha A F T
Author van Hijum, Sacha A F T Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands NIZO, 6710 BA Ede, The Netherlands
Rodenburg, Richard
Author Rodenburg, Richard Radboud Center for Mitochondrial Disorders, Translational Metabolic Laboratory, Department of Pediatrics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
van den Heuvel, Lambertus P
Author van den Heuvel, Lambertus P Department of Pediatrics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
van Spronsen, Francjan
Author van Spronsen, Francjan Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, PO BOX 30.001, 9700 RB Groningen, The Netherlands
Honzik, Tomas
Author Honzik, Tomas Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Foulquier, Francois
Author Foulquier, Francois CNRS-UMR 8576, Structural and Functional Glycobiology Unit, FRABIO, University of Lille, 59655 Villeneuve d'Ascq, France
van Scherpenzeel, Monique
Author van Scherpenzeel, Monique Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Lefeber, Dirk J
Author Lefeber, Dirk J Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
CDG group
Author CDG group
Mirjam, Wamelink
Author Mirjam, Wamelink Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Han, Brunner
Author Han, Brunner Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Helen, Mundy
Author Helen, Mundy Centre for Inherited Metabolic Disease, Evelina Children's Hospital, Guys and St Thomas NHS Foundation Trust, London SE1 7EH, UK
Helen, Michelakakis
Author Helen, Michelakakis Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece
Peter, van Hasselt
Author Peter, van Hasselt Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Jiddeke, van de Kamp
Author Jiddeke, van de Kamp Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
Diego, Martinelli
Author Diego, Martinelli Genetics and Rare Diseases Research Division, Bambino Gesù Children's Research Hospital, Rome, Italy
Lars, Morkrid
Author Lars, Morkrid Department of Medical Biochemistry, Oslo University Hospital, and Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Katja, Brocke Holmefjord
Author Katja, Brocke Holmefjord Department of Child Neurology, University Hospital Stavanger, Stavanger, Norway
Jozef, Hertecant
Author Jozef, Hertecant Department of Paediatrics, Tawam Hospital, Al-Ain, UAE
Majid, Alfadhel
Author Majid, Alfadhel King Abdullah International Medical Research Centre, King Saud bin Abdul Aziz University for Health Sciences, Division of Genetics, Department of Pediatrics, King Abdullah Specialized Children Hospital, King Abdul Aziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia
Kevin, Carpenter
Author Kevin, Carpenter NSW Biochemical Genetics Service, The Children's Hospital at Westmead, Disciplines of Genetic Medicine & Child and Adolescent Health, The University of Sydney, NSW 2145, Australia
Johann, Te Water Naude
Author Johann, Te Water Naude Department of Child Health, University Hospital of Wales, Cardiff, UK

Human molecular genetics. 2018 Sep 01 ; 27 (17) : 3029-3045.

Hum Mol Genet
ISSN 1460-2083 | 0964-6906
Source

Language English Country Great Britain, England Media print

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link https://www.medvik.cz/link/pmid29878199

PubMed 29878199
DOI 10.1093/hmg/ddy213
PII: 5033379
Knihovny.cz E-resources

MeSH
Zebrafish genetics growth & development metabolism MeSH
Adult MeSH
Exome MeSH
Phenotype MeSH
Fibroblasts metabolism pathology MeSH
Calcification, Physiologic * MeSH
Genomics * MeSH
Glycomics * MeSH
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase deficiency MeSH
Glycosylation MeSH
Golgi Apparatus metabolism pathology MeSH
Cohort Studies MeSH
Infant MeSH
Cells, Cultured MeSH
Humans MeSH
Young Adult MeSH
Mutation * MeSH
Organic Anion Transporters, Sodium-Dependent genetics metabolism MeSH
Pedigree MeSH
Symporters genetics metabolism MeSH
Protein Transport MeSH
Congenital Disorders of Glycosylation complications MeSH
Bone Diseases, Developmental etiology metabolism pathology MeSH
Animals MeSH
Check Tag
Adult MeSH
Infant MeSH
Humans MeSH
Young Adult MeSH
Male MeSH
Female MeSH
Animals MeSH
Publication type
Journal Article MeSH
Research Support, Non-U.S. Gov't MeSH
Names of Substances
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase MeSH
Organic Anion Transporters, Sodium-Dependent MeSH
Slc10a7 protein, human MeSH Browser
Symporters MeSH

Genomics methodologies have significantly improved elucidation of Mendelian disorders. The combination with high-throughput functional-omics technologies potentiates the identification and confirmation of causative genetic variants, especially in singleton families of recessive inheritance. In a cohort of 99 individuals with abnormal Golgi glycosylation, 47 of which being unsolved, glycomics profiling was performed of total plasma glycoproteins. Combination with whole-exome sequencing in 31 cases revealed a known genetic defect in 15 individuals. To identify additional genetic factors, hierarchical clustering of the plasma glycomics data was done, which indicated a subgroup of four patients that shared a unique glycomics signature of hybrid type N-glycans. In two siblings, compound heterozygous mutations were found in SLC10A7, a gene of unknown function in human. These included a missense mutation that disrupted transmembrane domain 4 and a mutation in a splice acceptor site resulting in skipping of exon 9. The two other individuals showed a complete loss of SLC10A7 mRNA. The patients' phenotype consisted of amelogenesis imperfecta, skeletal dysplasia, and decreased bone mineral density compatible with osteoporosis. The patients' phenotype was mirrored in SLC10A7 deficient zebrafish. Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization. Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane. In contrast to yeast, human SLC10A7 localized to the Golgi. Our combined data indicate an important role for SLC10A7 in bone mineralization and transport of glycoproteins to the extracellular matrix.

Center for Molecular and Biomolecular Informatics Radboud Institute for Molecular Life Sciences Radboud University Medical Center 6525 GA Nijmegen The Netherlands

Centre for Inherited Metabolic Disease Evelina Children's Hospital Guys and St Thomas NHS Foundation Trust London SE1 7EH UK

CNRS UMR 8576 Structural and Functional Glycobiology Unit FRABIO University of Lille 59655 Villeneuve d'Ascq France

Department of Child Health University Hospital of Wales Cardiff UK

Department of Child Neurology University Hospital Stavanger Stavanger Norway

Department of Clinical Chemistry VU University Medical Center Amsterdam The Netherlands

Department of Clinical Genetics VU University Medical Center Amsterdam The Netherlands

Department of Enzymology and Cellular Function Institute of Child Health Athens Greece

Department of Genetics University Medical Center Utrecht Utrecht The Netherlands

Department of Human Genetics Radboud University Medical Center 6525 GA Nijmegen The Netherlands

Department of Medical Biochemistry Oslo University Hospital and Faculty of Medicine Institute of Clinical Medicine University of Oslo Oslo Norway

Department of Medicine Physiology and Institute of Medical Science Faculty of Medicine University of Toronto ON Canada