CDG1G
MCID: CNG194
MIFTS: 39

Congenital Disorder of Glycosylation, Type Ig (CDG1G)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Liver diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases, Smell/Taste diseases

Aliases & Classifications for Congenital Disorder of Glycosylation, Type Ig

MalaCards integrated aliases for Congenital Disorder of Glycosylation, Type Ig:

Name: Congenital Disorder of Glycosylation, Type Ig 56 13
Alg12-Congenital Disorder of Glycosylation 12 25 29 6
Cdg1g 56 25 58 73
Congenital Disorder of Glycosylation Type 1g 25 58 71
Congenital Disorder of Glycosylation Type Ig 25 58 73
Cdg Ig 56 25 73
Congenital Disorder of Glycosylation 1g 12 73
Cdg-Ig 58 73
Cdgig 56 73
Carbohydrate Deficient Glycoprotein Syndrome Type Ig 58
Glycosylation, Congenital Disorder of, Type Ig 39
Congenital Disorder of Glycosylation Ig 12
Mannosyltransferase 8 Deficiency 58
Cdg Syndrome Type Ig 58
Cdg Ig; Cdgig 56
Alg12-Cdg 58

Characteristics:

Orphanet epidemiological data:

58
alg12-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
death in neonatal period or infancy
variable feature may be present


HPO:

31
congenital disorder of glycosylation, type ig:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Congenital Disorder of Glycosylation, Type Ig

Genetics Home Reference : 25 ALG12-congenital disorder of glycosylation (ALG12-CDG, also known as congenital disorder of glycosylation type Ig) is an inherited disorder with varying signs and symptoms that can affect several body systems. Individuals with ALG12-CDG typically develop signs and symptoms of the condition during infancy. They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). In addition, affected individuals often have intellectual disability, delayed development, and weak muscle tone (hypotonia), and some develop seizures. ALG12 ALG12 ALG12 Some people with ALG12-CDG have physical abnormalities such as a small head size (microcephaly) and unusual facial features. These features can include folds of skin that cover the inner corners of the eyes (epicanthal folds), a prominent nasal bridge, and abnormally shaped ears. Some males with ALG12-CDG have abnormal genitalia, such as a small penis (micropenis) and undescended testes. ALG12 ALG12 People with ALG12-CDG often produce abnormally low levels of proteins called antibodies (or immunoglobulins), particularly immunoglobulin G (IgG). Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies can make it difficult for affected individuals to fight infections. ALG12 Less common abnormalities seen in people with ALG12-CDG include a weakened heart muscle (cardiomyopathy) and poor bone development, which can lead to skeletal abnormalities. ALG12

MalaCards based summary : Congenital Disorder of Glycosylation, Type Ig, also known as alg12-congenital disorder of glycosylation, is related to congenital disorders of n-linked glycosylation and multiple pathway and alacrima, achalasia, and mental retardation syndrome. An important gene associated with Congenital Disorder of Glycosylation, Type Ig is ALG12 (ALG12 Alpha-1,6-Mannosyltransferase). The drugs Antithrombins and Antithrombin III have been mentioned in the context of this disorder. Affiliated tissues include bone, eye and heart, and related phenotypes are muscular hypotonia and cognitive impairment

Disease Ontology : 12 A congenital disorder of glycosylation I that is characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors and has material basis in homozygous or compound heterozygous mutation in the gene encoding dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase on chromosome 22q13.

OMIM : 56 Congenital disorders of glycosylation (CDG), previously called carbohydrate-deficient glycoprotein syndromes (CDGSs), are a group of hereditary multisystem disorders first recognized by Jaeken et al. (1980). The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing (IEF) of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. For a general discussion of CDGs, see CDG1A (212065) and CDG1B (602579). (607143)

UniProtKB/Swiss-Prot : 73 Congenital disorder of glycosylation 1G: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.

Related Diseases for Congenital Disorder of Glycosylation, Type Ig

Diseases in the Disorder of Multiple Glycosylation family:

Congenital Disorder of Glycosylation, Type Ia Congenital Disorder of Glycosylation, Type Iia
Congenital Disorder of Glycosylation, Type I/iix Congenital Disorder of Glycosylation, Type Iic
Congenital Disorder of Glycosylation, Type Iim Congenital Disorder of Glycosylation, Type Iy
Congenital Disorder of Glycosylation, Type Id Congenital Disorder of Glycosylation, Type Ib
Congenital Disorder of Glycosylation, Type Ic Congenital Disorder of Glycosylation, Type Iif
Congenital Disorder of Glycosylation, Type Iib Congenital Disorder of Glycosylation, Type Iid
Congenital Disorder of Glycosylation, Type Ig Congenital Disorder of Glycosylation, Type Ii
Congenital Disorder of Glycosylation, Type Ij Congenital Disorder of Glycosylation, Type Ih
Congenital Disorder of Glycosylation, Type Ik Congenital Disorder of Glycosylation, Type Il
Congenital Disorder of Glycosylation, Type Ie Congenital Disorder of Glycosylation, Type if
Congenital Disorder of Glycosylation, Type Im Congenital Disorder of Glycosylation, Type Iih
Congenital Disorder of Glycosylation, Type Iig Congenital Disorder of Glycosylation, Type in
Congenital Disorder of Glycosylation, Type Iq Congenital Disorder of Glycosylation, Type Iij
Congenital Disorder of Glycosylation, Type Iii Congenital Disorder of Glycosylation, Type Ip
Congenital Disorder of Glycosylation, Type Ir Congenital Disorder of Glycosylation, Type Iil
Congenital Disorder of Glycosylation, Type Iik Congenital Disorder of Glycosylation, Type It
Congenital Disorder of Glycosylation, Type Iu Congenital Disorder of Glycosylation, Type Iw
Congenital Disorder of Glycosylation, Type Ix Congenital Disorder of Glycosylation, Type Iin
Congenital Disorder of Glycosylation, Type Iio Congenital Disorder of Glycosylation, Type Iip
Congenital Disorder of Glycosylation, Type Iiq

Diseases related to Congenital Disorder of Glycosylation, Type Ig via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 congenital disorders of n-linked glycosylation and multiple pathway 10.3
2 alacrima, achalasia, and mental retardation syndrome 10.2
3 congenital disorder of glycosylation, type in 10.2
4 pseudodiastrophic dysplasia 10.1
5 skeletal dysplasias 10.1
6 retinitis pigmentosa 10.0
7 neuroretinitis 10.0
8 microcephaly 10.0
9 alternating exotropia 10.0
10 exotropia 10.0
11 retinitis 10.0
12 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 10.0
13 retinal detachment 10.0
14 yemenite deaf-blind hypopigmentation syndrome 10.0
15 branchiootic syndrome 1 10.0
16 hypospadias 10.0
17 clubfoot 10.0
18 agammaglobulinemia 10.0
19 polyhydramnios 10.0
20 hypoglycemia 10.0
21 hypertrophic cardiomyopathy 10.0
22 hypotonia 10.0

Graphical network of the top 20 diseases related to Congenital Disorder of Glycosylation, Type Ig:



Diseases related to Congenital Disorder of Glycosylation, Type Ig

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Ig

Human phenotypes related to Congenital Disorder of Glycosylation, Type Ig:

58 31 (show all 42)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
2 cognitive impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0100543
3 abnormality of immune system physiology 58 31 frequent (33%) Frequent (79-30%) HP:0010978
4 abnormality of the genital system 58 31 frequent (33%) Frequent (79-30%) HP:0000078
5 failure to thrive 31 HP:0001508
6 global developmental delay 31 HP:0001263
7 recurrent respiratory infections 31 HP:0002205
8 abnormal facial shape 31 HP:0001999
9 feeding difficulties 31 HP:0011968
10 cryptorchidism 31 HP:0000028
11 sensorineural hearing impairment 31 HP:0000407
12 polyhydramnios 31 HP:0001561
13 midface retrusion 31 HP:0011800
14 short philtrum 31 HP:0000322
15 generalized hypotonia 31 HP:0001290
16 edema 31 HP:0000969
17 patent ductus arteriosus 31 HP:0001643
18 inverted nipples 31 HP:0003186
19 decreased antibody level in blood 31 HP:0004313
20 abnormality of the pinna 31 HP:0000377
21 talipes equinovarus 31 HP:0001762
22 rhizomelia 31 HP:0008905
23 hypospadias 31 HP:0000047
24 thin upper lip vermilion 31 HP:0000219
25 micropenis 31 HP:0000054
26 hypocalcemia 31 HP:0002901
27 patent foramen ovale 31 HP:0001655
28 retinal detachment 31 HP:0000541
29 sandal gap 31 HP:0001852
30 scrotal hypoplasia 31 HP:0000046
31 wide nose 31 HP:0000445
32 butterfly vertebrae 31 HP:0003316
33 prolonged partial thromboplastin time 31 HP:0003645
34 hypoplasia of the radius 31 HP:0002984
35 respiratory tract infection 31 HP:0011947
36 small for gestational age 31 HP:0001518
37 short tibia 31 HP:0005736
38 short humerus 31 HP:0005792
39 short femur 31 HP:0003097
40 short ribs 31 HP:0000773
41 psychomotor retardation 31 HP:0025356
42 progressive microcephaly 31 HP:0000253

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Genitourinary Internal Genitalia Male:
cryptorchidism

Cardiovascular Vascular:
patent ductus arteriosus

Skeletal Feet:
talipes equinovarus
sandal gap
clubfoot
duplication of talus, bilateral

Cardiovascular Heart:
patent foramen ovale

Skeletal Limbs:
short tibia
short humerus
short femur
ulnar deviation
rhizomelic limb shortening
more
Head And Neck Mouth:
thin upper lip

Head And Neck Nose:
broad nose

Growth Weight:
low birth weight

Head And Neck Ears:
thick ears
sensorineural deafness (in 2 siblings)

Chest Ribs Sternum Clavicles And Scapulae:
short ribs with flared metaphyses

Skeletal Hands:
interphalangeal dislocations

Laboratory Abnormalities:
abnormal glycosylation of transferrin, type 1 pattern

Abdomen Gastrointestinal:
feeding difficulties

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Chest Breasts:
inverted nipples

Genitourinary External Genitalia Male:
hypospadias
micropenis
hypoplastic scrotum

Skeletal Spine:
butterfly vertebrae
delayed ossification of cervical vertebral bodies

Neurologic Central Nervous System:
psychomotor retardation
hypotonia

Head And Neck Face:
midface hypoplasia
facial dysmorphism

Immunology:
frequent respiratory infections
hypogammaglobulinemia

Head And Neck Head:
microcephaly, progressive

Head And Neck Eyes:
retinal detachment, bilateral (in 1 patient)

Skeletal Pelvis:
delayed ossification of pubic bone

Muscle Soft Tissue:
edema present at birth

Clinical features from OMIM:

607143

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Ig

Drugs for Congenital Disorder of Glycosylation, Type Ig (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antithrombins
2 Antithrombin III

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 "Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects" (CARDIoG) Unknown status NCT02503267

Search NIH Clinical Center for Congenital Disorder of Glycosylation, Type Ig

Genetic Tests for Congenital Disorder of Glycosylation, Type Ig

Genetic tests related to Congenital Disorder of Glycosylation, Type Ig:

# Genetic test Affiliating Genes
1 Alg12-Congenital Disorder of Glycosylation 29 ALG12

Anatomical Context for Congenital Disorder of Glycosylation, Type Ig

MalaCards organs/tissues related to Congenital Disorder of Glycosylation, Type Ig:

40
Bone, Eye, Heart, Skin, Testes, Liver

Publications for Congenital Disorder of Glycosylation, Type Ig

Articles related to Congenital Disorder of Glycosylation, Type Ig:

# Title Authors PMID Year
1
Abnormal glycosylation of red cell membrane band 3 in the congenital disorder of glycosylation Ig. 61 56 6
12736397 2003
2
Deficiency of dolichyl-P-Man:Man7GlcNAc2-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig. 61 56 6
12093361 2002
3
Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality. 56 6
17506107 2007
4
ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg. 56 6
12217961 2002
5
Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase. 56 6
11983712 2002
6
Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview 6
20301507 2005
7
Ocular abnormalities in a patient with congenital disorder of glycosylation type Ig. 61
31743061 2019
8
Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia. 61
25019053 2014
9
Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig. 61
15639192 2005

Variations for Congenital Disorder of Glycosylation, Type Ig

ClinVar genetic disease variations for Congenital Disorder of Glycosylation, Type Ig:

6 (show all 29) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ALG12 NM_024105.4(ALG12):c.424T>G (p.Phe142Val)SNV Pathogenic 3433 rs28942090 22:50304127-50304127 22:49910479-49910479
2 ALG12 NM_024105.4(ALG12):c.200C>T (p.Thr67Met)SNV Pathogenic 3434 rs121907931 22:50307128-50307128 22:49913480-49913480
3 ALG12 NM_024105.4(ALG12):c.437G>A (p.Arg146Gln)SNV Pathogenic 3435 rs121907932 22:50304114-50304114 22:49910466-49910466
4 ALG12 NM_024105.4(ALG12):c.301G>A (p.Gly101Arg)SNV Pathogenic 3436 rs121907933 22:50304250-50304250 22:49910602-49910602
5 ALG12 NM_024105.4(ALG12):c.473T>C (p.Leu158Pro)SNV Pathogenic 3437 rs121907934 22:50303733-50303733 22:49910085-49910085
6 ALG12 NM_024105.4(ALG12):c.1242C>G (p.Tyr414Ter)SNV Pathogenic 3438 rs121907935 22:50297711-50297711 22:49904063-49904063
7 ALG12 NM_024105.4(ALG12):c.1001del (p.Asn334fs)deletion Pathogenic 242854 rs759244819 22:50298146-50298146 22:49904498-49904498
8 ALG12 NM_024105.4(ALG12):c.117del (p.Gln40fs)deletion Pathogenic 242855 rs761221480 22:50307297-50307297 22:49913649-49913649
9 ALG12 NM_024105.4(ALG12):c.930_931del (p.Arg311fs)deletion Pathogenic 560937 rs1569174722 22:50301430-50301431 22:49907782-49907783
10 ALG12 NM_024105.4(ALG12):c.367G>A (p.Gly123Arg)SNV Likely pathogenic 523035 rs1555930118 22:50304184-50304184 22:49910536-49910536
11 ALG12 NM_024105.4(ALG12):c.1439T>C (p.Leu480Pro)SNV Likely pathogenic 637057 22:50297514-50297514 22:49903866-49903866
12 ALG12 NM_024105.4(ALG12):c.863C>T (p.Thr288Met)SNV Uncertain significance 640867 22:50301498-50301498 22:49907850-49907850
13 ALG12 NM_024105.4(ALG12):c.811G>A (p.Gly271Ser)SNV Uncertain significance 664837 22:50301550-50301550 22:49907902-49907902
14 ALG12 NM_024105.4(ALG12):c.809G>A (p.Arg270His)SNV Uncertain significance 654196 22:50301552-50301552 22:49907904-49907904
15 ALG12 NM_024105.4(ALG12):c.434C>T (p.Thr145Met)SNV Uncertain significance 656000 22:50304117-50304117 22:49910469-49910469
16 ALG12 NC_000022.10:g.(?_50297466)_(50301612_?)deldeletion Uncertain significance 661745 22:50297466-50301612 22:49903818-49907964
17 ALG12 NM_024105.4(ALG12):c.1048G>A (p.Gly350Arg)SNV Uncertain significance 471228 rs377095724 22:50298099-50298099 22:49904451-49904451
18 ALG12 NM_024105.4(ALG12):c.644C>T (p.Pro215Leu)SNV Uncertain significance 548599 rs777173365 22:50303562-50303562 22:49909914-49909914
19 ALG12 NM_024105.4(ALG12):c.931C>T (p.Arg311Cys)SNV Uncertain significance 377465 rs746215829 22:50301430-50301430 22:49907782-49907782
20 ALG12 NM_024105.4(ALG12):c.671C>T (p.Thr224Met)SNV Uncertain significance 471230 rs755892540 22:50302989-50302989 22:49909341-49909341
21 ALG12 NM_024105.4(ALG12):c.1446G>C (p.Glu482Asp)SNV Uncertain significance 571776 rs1569172835 22:50297507-50297507 22:49903859-49903859
22 ALG12 NM_024105.4(ALG12):c.652A>G (p.Ile218Val)SNV Uncertain significance 578572 rs146322225 22:50303554-50303554 22:49909906-49909906
23 ALG12 NM_024105.4(ALG12):c.469+4C>TSNV Uncertain significance 581338 rs555319649 22:50304078-50304078 22:49910430-49910430
24 ALG12 NM_024105.4(ALG12):c.1082C>T (p.Thr361Met)SNV Uncertain significance 594408 rs748537273 22:50298065-50298065 22:49904417-49904417
25 ALG12 NM_024105.4(ALG12):c.1244A>G (p.Asp415Gly)SNV Uncertain significance 597467 rs201717237 22:50297709-50297709 22:49904061-49904061
26 ALG12 NM_024105.4(ALG12):c.622A>T (p.Arg208Ter)SNV Uncertain significance 631900 rs1464756874 22:50303584-50303584 22:49909936-49909936
27 ALG12 NM_024105.4(ALG12):c.207C>T (p.Leu69=)SNV Likely benign 471229 rs765297992 22:50307121-50307121 22:49913473-49913473
28 ALG12 NM_024105.4(ALG12):c.99G>A (p.Val33=)SNV Benign/Likely benign 342060 rs76707654 22:50307315-50307315 22:49913667-49913667
29 ALG12 NM_024105.4(ALG12):c.1029G>A (p.Ala343=)SNV Benign/Likely benign 342045 rs62233155 22:50298118-50298118 22:49904470-49904470

UniProtKB/Swiss-Prot genetic disease variations for Congenital Disorder of Glycosylation, Type Ig:

73
# Symbol AA change Variation ID SNP ID
1 ALG12 p.Thr67Met VAR_017904 rs121907931
2 ALG12 p.Phe142Val VAR_017905 rs28942090
3 ALG12 p.Arg146Gln VAR_017906 rs121907932
4 ALG12 p.Leu158Pro VAR_017907 rs121907934
5 ALG12 p.Gly101Arg VAR_038428 rs121907933

Expression for Congenital Disorder of Glycosylation, Type Ig

Search GEO for disease gene expression data for Congenital Disorder of Glycosylation, Type Ig.

Pathways for Congenital Disorder of Glycosylation, Type Ig

GO Terms for Congenital Disorder of Glycosylation, Type Ig

Sources for Congenital Disorder of Glycosylation, Type Ig

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
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30 HMDB
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32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
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48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
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72 UMLS via Orphanet
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