Table 2.
Golgi-related glycosylation disorders
| Gene function | Gene | OMIM | Clinical presentation | |
|---|---|---|---|---|
| N-glycan disorders | ||||
| MGAT2-CDG (CDG-IIa)a | N-acetylglucosaminyltransferase II | MGAT2 | 212066 | Mental retardation, dysmorphism, seizures |
| I-cell disease | GlcNAc-1-P transferase | GNPTA | 252500 | Severe developmental abnormalities |
| Multiple pathway disorders | ||||
| SLC35C1-CDG (CDG-IIc)a | GDP-fucose transporter | FUCT1 | 266265 | Severe psychomotor retardation, hypotonia, elevated peripheral neutrophils |
| B4GALT1-CDG (CDG-IId)a | β1,4-galactosyltransferase | B4GALT1 | 607091 | Hypotonia, spontaneous hemorrhage, Dandy–Walker malformation |
| COG7-CDG (CDG-IIe)a | Conserved oligomeric Golgi subunit 7 | COG7 | 608779 | Early death, dysmorphism, hypotonia, seizures, hepatomegaly, recurrent infections, cardiac failure, excessive skin |
| SLC35A1-CDG (CDG-IIf)a | CMP-sialic acid transporter | SLC35A1 | 605634 | Normal transferrin, thrombocytopaenia, abnormal platelet glycoproteins |
| COG1-CDG (CDG-IIh)a | Conserved oligomeric Golgi subunit 1 | COG1 | 606973 | Mild MR, hypotonia, growth retardation, progressive microcephaly, hepatosplenomegaly |
| COG8-CDG | Conserved oligomeric Golgi subunit 8 | COG8 | 611182 | MR, hypotonia, encephalopathy |
| COG5-CDG | Conserved oligomeric Golgi subunit 5 | COG5 | — | Moderate mental retardation with cerebellar atrophy, hypotonia |
| COG4-CDG | Conserved oligomeric Golgi subunit 4 | COG4 | — | Mild mental retardation, mild dysmorphia, epilepsy, recurrent respiratory infections, mild ataxia |
| COG6-CDG | Conserved oligomeric Golgi subunit 6 | COG6 | — | Early fatality, severe neurological impairment, seizures, vomiting, intracranial bleeding, |
| ATP6V0A2-CDG | Golgi pH regulator | ATP6V0A2 | 219200 | Cutis laxa, wrinkly skin, connective tissue weakness, large fontanelle, variable mental retardation |
| Achondrogenesis type 1A | Golgi structure | GMAP210 | 200600 | Soft skull bones, short ribs that fracture easily, extremely short limbs, and lack normal ossification in the spine and pelvis |
| Gerodermia Osteodysplastica | Golgi structure | SCYL1BP1 | 231070 | Wrinkley lax skin, osteoporosis, variable growth retardation |
| Congenital dyserythropoietic anemia (CDA II) | ER-Golgi protein trafficking | SEC23B | 224100 | Anemia, jaundice, splenomegaly, gall bladder disease |
| Cranio-lenticulo-sutural dysplasia (CLSD) | ER-Golgi protein trafficking | SEC23A | 607812 | Facial dysmorphisms, sutural cataracts and skeletal defects |
| O-mannose disorders (dystroglycanopathy) | ||||
| Walker–Warburg syndrome | O-mannosyltransferase | POMT1, POMT2 | 268870 | Death in infancy, severe muscle weakness, diminished psychomotor development, abnormal neuronal migration ocular abnormalities |
| Muscle–eye–brain disease (MEB) | O-mannosyl GlcNAc transferase | POMGnT1 | 253280 | Severe muscle weakness, mental retardation, epilepsy, neuronal migration disorder, ocular abnormalities |
| Fukuyama-type congenital muscular dystrophy (FCMD) | Putative glycosyltransferase | Fukutin | 253800 | Severe proximal and axial weakness, mental retardation, epilepsy and abnormal neuronal migration |
| Congenital muscular dystrophy type 1C (MDC1C) | Fukutin-related protein, a putative glycosyltransferase | FKRP | 606612 | Hypotonia, impaired motor development with respiratory muscle weakness |
| Congenital muscular dystrophy type 1D (MDC1D) | Putative glycosyltransferase | LARGE | 608840 | Muscular dystrophy with severe mental retardation |
| Glycophosphatidyl inositol disorders | ||||
| Autosomal Recessive GPI Anchor Deficiency | 1st mannosyltransferase in GPI biosynthesis | PIGM | 610273 | Venous thrombosis and seizures |
| Hyperphosphatasia mental retardation (HPMR) syndrome | 2nd mannosyltransferase in GPI biosynthesis | PIGV | 239300 | Hyperphosphatasia, mental retardation, and distinct facial characteristics |
| Glycosphingolipid disorders | ||||
| Amish infantile epilepsy | Sia2,3Galβ1,4Glc-Cer synthase (GM3) | SIAT9 | 609056 | Neurological decline with tonic-clonic seizures and arrested development |
| Glycosaminoglycan synthesis disorders (O-xylose) | ||||
| Multiple hereditary exostoses | Heparan sulfate copolymerase | EXT1, EXT2 | 133701 | Bony outgrowths |
| Ehlers–Danlos syndrome progeroid form | Xylosylprotein β-1,4-galactosyltransferase | B4GALT7 | 604327 130070 | Connective tissue abnormalities with loose skin, hypotonia and developmental delay |
| Diastrophic dysplasia achondrogenesis | Anion (sulfate) transporter | DTDST | 600972 606718 | Premature calcification, scoliosis, club foot |
| Spondylo-epimetaphyseal dysplasia | 3′-phosphoadenosine- 5′-phosphosulphate synthase (PAPS) | ATPSK2 | 603005 | Abnormal skeletal development and linear growth |
| Spondylo-epimetaphyseal dysplasia (Omani type) | Chondroitin 6-O-sulfotransferase | CHST3 | 143095 608637 | Normal intelligence, reduced adult height, progressive kyphoscoliosis, joint dislocations, cardiac involvement, mild brachydactyly, camptodactyly, and microdontia |
| Macular corneal dystrophy | GlcNAc-6-sulfotransferase | CHST6 | 605294 | Progressive corneal opacity. |
| Adducted thumb-clubfoot syndrome | N-acetylgalactosamine 4-O-sulfotransferase 1 | CHST14 | 601776 | Congenital contractures of thumbs and feet with joint instability, facial clefting, coagulopathy, abnormal skin, heart, kidney, or intestinal defects |
| Schneckenbecken dysplasia | UDP-GlcA / UDP-GalNAc Golgi transporter | SLC35D1 | 610804 | Severely shortened long bones with bowing of limb bones and unossified vertebral bodies |
| O-GalNAc disorders | ||||
| Familial tumoral calcinosis | GalNAc transferase | GALNT3 | 211900 | Large calcium deposits in both skin and tissue |
| Tn syndrome | Chaperone of β1,3GalT | COSMC | 230430 | Hematological abnormalities including anemia, leucopenia, thrombocytopaenia |
| O-fucose disorders | ||||
| Peters plus syndrome | β-1,3 glucosyltransferase specific for O-fucose on thrombospondin type 1 repeats | B3GALTL | 261540 | Mental retardation with prenatal growth delay, short stature, brachymorphism, short limbs, and eye abnormalities |
aData adapted from Jaeken et al. 2009.