title: GOLGA2, encoding a master regulator of golgi apparatus, is mutated in a patient with a neuromuscular disorder.
abstract: Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity. Many Mendelian diseases are caused by mutations in genes encoding various components of GA. GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex, and its deficiency has been found to result in severe cellular phenotypes. We describe the first human patient with a homozygous apparently loss of function mutation in GOLGA2. The phenotype is a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy. Knockdown of golga2 in zebrafish resulted in severe skeletal muscle disorganization and microcephaly recapitulating loss of function human phenotype. Our data suggest an important developmental role of GM130 in humans and zebrafish.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.affiliation: Division of Genetics, Brigham and Women's Hospital and Department of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Alexis H
authors.initials: AH
authors.lastname: Bennett
authors.affiliation: Genetics Division, Department of Pediatrics, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Majid
authors.initials: M
authors.lastname: Alfadhel
authors.affiliation: Division of Genetics, Brigham and Women's Hospital and Department of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D059472:Exome; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study / Q000379:methods; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008831:Microcephaly / Q000235:genetics; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D001324:Autoantigens; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins; D060172:Morpholinos; D012333:RNA, Messenger