CDG1G
MCID: CNG194
MIFTS: 38

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

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 57 13
Alg12-Congenital Disorder of Glycosylation 12 25 29 6
Cdg1g 57 25 59 74
Congenital Disorder of Glycosylation Type 1g 25 59 72
Congenital Disorder of Glycosylation Type Ig 25 59 74
Cdg Ig 57 25 74
Congenital Disorder of Glycosylation 1g 12 74
Cdg-Ig 59 74
Cdgig 57 74
Carbohydrate Deficient Glycoprotein Syndrome Type Ig 59
Glycosylation, Congenital Disorder of, Type Ig 40
Congenital Disorder of Glycosylation Ig 12
Mannosyltransferase 8 Deficiency 59
Cdg Syndrome Type Ig 59
Cdg Ig; Cdgig 57
Alg12-Cdg 59

Characteristics:

Orphanet epidemiological data:

59
alg12-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
congenital disorder of glycosylation, type ig:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080559
MeSH 44 D018981
ICD10 via Orphanet 34 E77.8
UMLS via Orphanet 73 C2931001
Orphanet 59 ORPHA79324
UMLS 72 C2931001

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 pseudodiastrophic dysplasia. An important gene associated with Congenital Disorder of Glycosylation, Type Ig is ALG12 (ALG12 Alpha-1,6-Mannosyltransferase). The drugs Antithrombin III and Antithrombins have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and skin, 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 : 57 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 : 74 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 16)
# Related Disease Score Top Affiliating Genes
1 congenital disorders of n-linked glycosylation and multiple pathway 10.2
2 pseudodiastrophic dysplasia 10.2
3 skeletal dysplasias 10.2
4 congenital disorder of glycosylation, type in 10.0
5 microcephaly 10.0
6 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 10.0
7 retinal detachment 10.0
8 yemenite deaf-blind hypopigmentation syndrome 10.0
9 branchiootic syndrome 1 10.0
10 hypospadias 10.0
11 agammaglobulinemia 10.0
12 polyhydramnios 10.0
13 hypoglycemia 10.0
14 hypertrophic cardiomyopathy 10.0
15 talipes equinovarus 10.0
16 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:

59 32 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
2 cognitive impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0100543
3 abnormality of immune system physiology 59 32 frequent (33%) Frequent (79-30%) HP:0010978
4 abnormality of the genital system 59 32 frequent (33%) Frequent (79-30%) HP:0000078
5 failure to thrive 32 HP:0001508
6 global developmental delay 32 HP:0001263
7 recurrent respiratory infections 32 HP:0002205
8 abnormal facial shape 32 HP:0001999
9 sensorineural hearing impairment 32 HP:0000407
10 short philtrum 32 HP:0000322
11 generalized hypotonia 32 HP:0001290
12 feeding difficulties 32 HP:0011968
13 patent ductus arteriosus 32 HP:0001643
14 cryptorchidism 32 HP:0000028
15 inverted nipples 32 HP:0003186
16 decreased antibody level in blood 32 HP:0004313
17 abnormality of the pinna 32 HP:0000377
18 talipes equinovarus 32 HP:0001762
19 rhizomelia 32 HP:0008905
20 hypospadias 32 HP:0000047
21 retinal detachment 32 HP:0000541
22 micropenis 32 HP:0000054
23 polyhydramnios 32 HP:0001561
24 sandal gap 32 HP:0001852
25 hypocalcemia 32 HP:0002901
26 thin upper lip vermilion 32 HP:0000219
27 midface retrusion 32 HP:0011800
28 butterfly vertebrae 32 HP:0003316
29 wide nose 32 HP:0000445
30 scrotal hypoplasia 32 HP:0000046
31 hypoplasia of the radius 32 HP:0002984
32 prolonged partial thromboplastin time 32 HP:0003645
33 small for gestational age 32 HP:0001518
34 patent foramen ovale 32 HP:0001655
35 short tibia 32 HP:0005736
36 short humerus 32 HP:0005792
37 short femur 32 HP:0003097
38 progressive microcephaly 32 HP:0000253
39 respiratory tract infection 32 HP:0011947
40 psychomotor retardation 32 HP:0025356

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Cardiovascular Vascular:
patent ductus arteriosus

Chest Breasts:
inverted nipples

Genitourinary External Genitalia Male:
hypospadias
micropenis
hypoplastic scrotum

Skeletal Spine:
butterfly vertebrae
delayed ossification of cervical vertebral bodies

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

Genitourinary Internal Genitalia Male:
cryptorchidism

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

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Cardiovascular Heart:
patent foramen ovale

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 Antithrombin III
2 Antithrombins

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:

41
Heart, Bone, Skin, Testes, Eye

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. 38 8 71
12736397 2003
2
Deficiency of dolichyl-P-Man:Man7GlcNAc2-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig. 38 8 71
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. 8 71
17506107 2007
4
ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg. 8 71
12217961 2002
5
Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase. 8 71
11983712 2002
6
Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview 71
20301507 2005
7
Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia. 38
25019053 2014
8
Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig. 38
15639192 2005

Variations for Congenital Disorder of Glycosylation, Type Ig

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

6 (show all 30)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ALG12 NM_024105.4(ALG12): c.930_931del (p.Arg311fs) deletion Pathogenic 22:50301429-50301431 22:49907782-49907783
2 ALG12 NM_024105.4(ALG12): c.424T> G (p.Phe142Val) single nucleotide variant Pathogenic rs28942090 22:50304127-50304127 22:49910479-49910479
3 ALG12 NM_024105.4(ALG12): c.200C> T (p.Thr67Met) single nucleotide variant Pathogenic rs121907931 22:50307128-50307128 22:49913480-49913480
4 ALG12 NM_024105.4(ALG12): c.437G> A (p.Arg146Gln) single nucleotide variant Pathogenic rs121907932 22:50304114-50304114 22:49910466-49910466
5 ALG12 NM_024105.4(ALG12): c.301G> A (p.Gly101Arg) single nucleotide variant Pathogenic rs121907933 22:50304250-50304250 22:49910602-49910602
6 ALG12 NM_024105.4(ALG12): c.473T> C (p.Leu158Pro) single nucleotide variant Pathogenic rs121907934 22:50303733-50303733 22:49910085-49910085
7 ALG12 NM_024105.4(ALG12): c.1242C> G (p.Tyr414Ter) single nucleotide variant Pathogenic rs121907935 22:50297711-50297711 22:49904063-49904063
8 ALG12 NM_024105.4(ALG12): c.1001del (p.Asn334fs) deletion Pathogenic rs759244819 22:50298146-50298146 22:49904498-49904498
9 ALG12 NM_024105.4(ALG12): c.117del (p.Gln40fs) deletion Pathogenic rs761221480 22:50307297-50307297 22:49913649-49913649
10 ALG12 NM_024105.4(ALG12): c.367G> A (p.Gly123Arg) single nucleotide variant Likely pathogenic rs1555930118 22:50304184-50304184 22:49910536-49910536
11 ALG12 NM_024105.4(ALG12): c.1439T> C (p.Leu480Pro) single nucleotide variant Likely pathogenic 22:50297514-50297514 22:49903866-49903866
12 ALG12 NM_024105.4(ALG12): c.863C> T (p.Thr288Met) single nucleotide variant Uncertain significance 22:50301498-50301498 22:49907850-49907850
13 ALG12 NM_024105.4(ALG12): c.811G> A (p.Gly271Ser) single nucleotide variant Uncertain significance 22:50301550-50301550 22:49907902-49907902
14 ALG12 NM_024105.4(ALG12): c.809G> A (p.Arg270His) single nucleotide variant Uncertain significance 22:50301552-50301552 22:49907904-49907904
15 ALG12 NM_024105.4(ALG12): c.434C> T (p.Thr145Met) single nucleotide variant Uncertain significance 22:50304117-50304117 22:49910469-49910469
16 ALG12 NC_000022.10: g.(?_50297466)_(50301612_?)del deletion Uncertain significance 22:50297466-50301612 22:49903818-49907964
17 ALG12 NM_024105.4(ALG12): c.1446G> C (p.Glu482Asp) single nucleotide variant Uncertain significance 22:50297507-50297507 22:49903859-49903859
18 ALG12 NM_024105.4(ALG12): c.652A> G (p.Ile218Val) single nucleotide variant Uncertain significance 22:50303554-50303554 22:49909906-49909906
19 ALG12 NM_024105.4(ALG12): c.469+4C> T single nucleotide variant Uncertain significance 22:50304078-50304078 22:49910430-49910430
20 ALG12 NM_024105.4(ALG12): c.1082C> T (p.Thr361Met) single nucleotide variant Uncertain significance 22:50298065-50298065 22:49904417-49904417
21 ALG12 NM_024105.4(ALG12): c.1244A> G (p.Asp415Gly) single nucleotide variant Uncertain significance 22:50297709-50297709 22:49904061-49904061
22 ALG12 NM_024105.4(ALG12): c.622A> T (p.Arg208Ter) single nucleotide variant Uncertain significance 22:50303584-50303584 22:49909936-49909936
23 ALG12 NM_024105.4(ALG12): c.644C> T (p.Pro215Leu) single nucleotide variant Uncertain significance rs777173365 22:50303562-50303562 22:49909914-49909914
24 ALG12 NM_024105.4(ALG12): c.931C> T (p.Arg311Cys) single nucleotide variant Uncertain significance rs746215829 22:50301430-50301430 22:49907782-49907782
25 ALG12 NM_024105.4(ALG12): c.671C> T (p.Thr224Met) single nucleotide variant Uncertain significance rs755892540 22:50302989-50302989 22:49909341-49909341
26 ALG12 NM_024105.4(ALG12): c.1048G> A (p.Gly350Arg) single nucleotide variant Uncertain significance rs377095724 22:50298099-50298099 22:49904451-49904451
27 ALG12 NM_024105.4(ALG12): c.207C> T (p.Leu69=) single nucleotide variant Likely benign rs765297992 22:50307121-50307121 22:49913473-49913473
28 ALG12 NM_024105.4(ALG12): c.1029G> A (p.Ala343=) single nucleotide variant Benign/Likely benign rs62233155 22:50298118-50298118 22:49904470-49904470
29 ALG12 NM_024105.4(ALG12): c.99G> A (p.Val33=) single nucleotide variant Benign/Likely benign rs76707654 22:50307315-50307315 22:49913667-49913667
30 ALG12 NM_024105.4(ALG12): c.631C> T (p.Arg211Cys) single nucleotide variant Benign rs144665682 22:50303575-50303575 22:49909927-49909927

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

74
# 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

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7 CNVD
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10 dbSNP
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36 IUPHAR
37 KEGG
38 LifeMap
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44 MeSH
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54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
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73 UMLS via Orphanet
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