CCDC115 Deficiency Causes a Disorder of ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation
Auteur(s) :
Jansen, Jos C. [Auteur]
Cirak, Sebahattin [Auteur]
van Scherpenzeel, Monique [Auteur]
Timal, Sharita [Auteur]
Reunert, Janine [Auteur]
Rust, Stephan [Auteur]
Pérez, Belén [Auteur]
Vicogne, Dorothee [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Krawitz, Peter [Auteur]
Wada, Yoshinao [Auteur]
Ashikov, Angel [Auteur]
Pérez-Cerdá, Celia [Auteur]
Medrano, Celia [Auteur]
Arnoldy, Andrea [Auteur]
Hoischen, Alexander [Auteur]
Huijben, Karin [Auteur]
Steenbergen, Gerry [Auteur]
Quelhas, Dulce [Auteur]
Diogo, Luisa [Auteur]
Rymen, Daisy [Auteur]
Jaeken, Jaak [Auteur]
Guffon, Nathalie [Auteur]
Cheillan, David [Auteur]
van den Heuvel, Lambertus P. [Auteur]
Maeda, Yusuke [Auteur]
Kaiser, Olaf [Auteur]
Schara, Ulrike [Auteur]
Gerner, Patrick [Auteur]
van den Boogert, Marjolein A. W. [Auteur]
Holleboom, Adriaan G. [Auteur]
Nassogne, Marie-Cécile [Auteur]
Sokal, Etienne [Auteur]
Salomon, Jody [Auteur]
van den Bogaart, Geert [Auteur]
Drenth, Joost P. H. [Auteur]
Huynen, Martijn A. [Auteur]
Veltman, Joris A. [Auteur]
Wevers, Ron A. [Auteur]
Morava, Eva [Auteur]
Matthijs, Gert [Auteur]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Marquardt, Thorsten [Auteur]
Lefeber, Dirk J. [Auteur]
Cirak, Sebahattin [Auteur]
van Scherpenzeel, Monique [Auteur]
Timal, Sharita [Auteur]
Reunert, Janine [Auteur]
Rust, Stephan [Auteur]
Pérez, Belén [Auteur]
Vicogne, Dorothee [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Krawitz, Peter [Auteur]
Wada, Yoshinao [Auteur]
Ashikov, Angel [Auteur]
Pérez-Cerdá, Celia [Auteur]
Medrano, Celia [Auteur]
Arnoldy, Andrea [Auteur]
Hoischen, Alexander [Auteur]
Huijben, Karin [Auteur]
Steenbergen, Gerry [Auteur]
Quelhas, Dulce [Auteur]
Diogo, Luisa [Auteur]
Rymen, Daisy [Auteur]
Jaeken, Jaak [Auteur]
Guffon, Nathalie [Auteur]
Cheillan, David [Auteur]
van den Heuvel, Lambertus P. [Auteur]
Maeda, Yusuke [Auteur]
Kaiser, Olaf [Auteur]
Schara, Ulrike [Auteur]
Gerner, Patrick [Auteur]
van den Boogert, Marjolein A. W. [Auteur]
Holleboom, Adriaan G. [Auteur]
Nassogne, Marie-Cécile [Auteur]
Sokal, Etienne [Auteur]
Salomon, Jody [Auteur]
van den Bogaart, Geert [Auteur]
Drenth, Joost P. H. [Auteur]
Huynen, Martijn A. [Auteur]
Veltman, Joris A. [Auteur]
Wevers, Ron A. [Auteur]
Morava, Eva [Auteur]
Matthijs, Gert [Auteur]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Marquardt, Thorsten [Auteur]
Lefeber, Dirk J. [Auteur]
Titre de la revue :
American journal of human genetics
Nom court de la revue :
Am. J. Hum. Genet.
Numéro :
98
Pagination :
310-321
Date de publication :
2016-02-04
ISSN :
1537-6605
Mot(s)-clé(s) en anglais :
Humans
Child, Preschool
Molecular Sequence Data
Homeostasis
hepatosplenomegaly
Male
Infant
Endoplasmic Reticulum
Alkaline Phosphatase
V-ATPase assembly
Exome
Cloning, Molecular
Fibroblasts
Female
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Child
Amino Acid Sequence
Golgi homeostasis
Glycosylation
Nerve Tissue Proteins
Vma22p
Golgi Apparatus
Phenotype
Pedigree
Heterozygote
HeLa Cells
Child, Preschool
Molecular Sequence Data
Homeostasis
hepatosplenomegaly
Male
Infant
Endoplasmic Reticulum
Alkaline Phosphatase
V-ATPase assembly
Exome
Cloning, Molecular
Fibroblasts
Female
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Child
Amino Acid Sequence
Golgi homeostasis
Glycosylation
Nerve Tissue Proteins
Vma22p
Golgi Apparatus
Phenotype
Pedigree
Heterozygote
HeLa Cells
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. ...
Lire la suite >Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal glycosylation in plasma.Lire moins >
Lire la suite >Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal glycosylation in plasma.Lire moins >
Langue :
Anglais
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
Mécanismes moléculaires de la N-glycosylation et pathologies associées
Date de dépôt :
2020-02-12T16:20:23Z