CDG2A
MCID: CNG191
MIFTS: 47

Congenital Disorder of Glycosylation, Type Iia (CDG2A)

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 Iia

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

Name: Congenital Disorder of Glycosylation, Type Iia 57 12 13
Congenital Disorder of Glycosylation Type Iia 12 59 75 15
Cdg2a 57 12 59 75
Carbohydrate-Deficient Glycoprotein Syndrome Type Ii 75 29 6
Cdg Iia 57 12 75
Cdgiia 57 12 75
Mental Retardation, Growth Retardation, Prominent Columella, and Open Mouth 57 12
Carbohydrate-Deficient Glycoprotein Syndrome, Type Ii 12 55
Congenital Disorder of Glycosylation Type 2a 59 73
Alkuraya Syndrome 57 12
Cdg-Iia 59 75
Carbohydrate-Deficient Glycoprotein Syndrome, Type Ii, Formerly; Cdgs2, Formerly 57
Carbohydrate-Deficient Glycoprotein Syndrome, Type Ii, Formerly 57
Carbohydrate Deficient Glycoprotein Syndrome Type Iia 59
Glycosylation, Congenital Disorder of, Type Iia 40
N-Acetylglucosaminyltransferase 2 Deficiency 59
Congenital Disorder of Glycosylation 2a 75
Cdg Syndrome Type Iia 59
Cdg Iia; Cdgiia 57
Cdgs2, Formerly 57
Cdgs Type Ii 75
Mgat2-Cdg 59
Cdgs2 12

Characteristics:

Orphanet epidemiological data:

59
mgat2-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
four individual patients and 1 saudi family have been reported (as of february 2012)


HPO:

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


Classifications:



Summaries for Congenital Disorder of Glycosylation, Type Iia

OMIM : 57 Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. These glycoconjugates play critical roles in metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity, among others. CDGs are divided into 2 main groups: type I CDGs (see, e.g., CDG1A, 212065) comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs refer to defects in the trimming and processing of the protein-bound glycans either late in the endoplasmic reticulum or the Golgi compartments. The biochemical changes of CDGs are most readily observed in serum transferrin (TF; 190000), and the diagnosis is usually made by isoelectric focusing of this glycoprotein (reviews by Marquardt and Denecke, 2003; Grunewald et al., 2002). (212066)

MalaCards based summary : Congenital Disorder of Glycosylation, Type Iia, also known as congenital disorder of glycosylation type iia, is related to congenital disorder of glycosylation, type ii and congenital disorder of glycosylation, type iik, and has symptoms including seizures An important gene associated with Congenital Disorder of Glycosylation, Type Iia is MGAT2 (Mannosyl (Alpha-1,6-)-Glycoprotein Beta-1,2-N-Acetylglucosaminyltransferase), and among its related pathways/superpathways are Metabolism of proteins and Transport to the Golgi and subsequent modification. Affiliated tissues include bone, skin and liver, and related phenotypes are intellectual disability, severe and intellectual disability, progressive

Disease Ontology : 12 A congenital disorder of glycosylation type II that has material basis in an autosomal recessive mutation of MGAT2 on chromosome 14q21.3.

UniProtKB/Swiss-Prot : 75 Congenital disorder of glycosylation 2A: 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 Iia

Diseases in the Congenital Disorder of Glycosylation, Type in 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 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 Iia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)
# Related Disease Score Top Affiliating Genes
1 congenital disorder of glycosylation, type ii 31.7 ALG2 MGAT2 PMM2 TF
2 congenital disorder of glycosylation, type iik 31.3 TF PMM2
3 congenital disorder of glycosylation, type ia 31.3 TF PMM2
4 congenital disorder of glycosylation, type iim 31.2 ALG2 PMM2 TF
5 congenital disorder of glycosylation, type in 29.4 TF PMM2 MPI MPDU1 MGAT2 ALG2
6 man1b1-cdg 11.6
7 cutis laxa, autosomal recessive, type iia 11.1
8 neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures 11.1
9 congenital disorder of glycosylation, type iic 11.0
10 congenital disorder of glycosylation, type iil 11.0
11 congenital disorder of glycosylation, type iin 11.0
12 congenital disorder of glycosylation, type iip 11.0
13 congenital disorder of glycosylation with defective fucosylation 11.0
14 autosomal recessive disease 10.1
15 epileptic encephalopathy, early infantile, 36 9.9 ALG2 MPI PMM2
16 carbohydrate metabolic disorder 9.9 ALG2 MPI PMM2
17 congenital disorder of glycosylation, type ie 9.9 PMM2 DPM1
18 multiple congenital anomalies-hypotonia-seizures syndrome 3 9.9 TF PMM2
19 congenital disorder of glycosylation, type iih 9.9 TF ALG2
20 congenital disorder of glycosylation, type iii 9.8 ALG2 PMM2 TF
21 congenital disorder of glycosylation, type iif 9.8 ALG2 PMM2 TF
22 fructose intolerance, hereditary 9.8 ALG2 PMM2 TF
23 congenital hemolytic anemia 9.8 TF SEC23B
24 uremia 9.7 VWF TF
25 congenital disorder of glycosylation, type iid 9.6 MPI PMM2 TF ALG2

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



Diseases related to Congenital Disorder of Glycosylation, Type Iia

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Iia

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly
microcephaly
brachycephaly

Chest External Features:
pectus excavatum

Neurologic Central Nervous System:
seizures
unsteady gait
mental retardation, severe
early hypotonia
later hypertonia

Skeletal Feet:
pes planus
irregular position of the toes

Head And Neck Face:
retrognathia
malar underdevelopment
obtuse lower incisor mandibular plane angle

Head And Neck Nose:
prominent nasal bridge
low hanging columella
hook nose

Cardiovascular Heart:
ventricular septal defect

Skin Nails Hair Hair:
long eyelashes
thick eyebrows
sparse hair (in some patients)
hirsutism (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
self-mutilation
aggression
stereotypic behaviors (hand-washing movements, head-banging)

Head And Neck Teeth:
diastema
large teeth

Skeletal Limbs:
gracile long bones

Hematology:
decreased coagulation factors ix, xi, xii
decreased antithrombin iii
decreased protein s
decreased protein c

Head And Neck Neck:
short neck

Skeletal:
osteopenia

Growth Other:
failure to thrive
postnatal growth retardation

Growth Height:
short stature

Skeletal Pelvis:
coxa valga

Head And Neck Mouth:
open mouth
protruding tongue
large mouth
thin lips
everted lower lip
more
Head And Neck Eyes:
long eyelashes
downslanting palpebral fissures
thick eyebrows

Head And Neck Ears:
posteriorly rotated ears
hearing loss, sensorineural
large dysplastic ears

Skeletal Spine:
thoracolumbar kyphoscoliosis

Skeletal Hands:
proximally placed thumbs
short terminal phalanges

Skin Nails Hair Skin:
midfrontal capillary hemangioma

Laboratory Abnormalities:
abnormal isoelectric focusing of serum transferrin (type 2 pattern)
glcnac-transferase ii deficiency in fibroblast and mononuclear cells


Clinical features from OMIM:

212066

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

59 32 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
2 intellectual disability, progressive 59 32 hallmark (90%) Very frequent (99-80%) HP:0006887
3 tall stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0000098
4 macrocephaly 32 HP:0000256
5 short neck 32 HP:0000470
6 pectus excavatum 32 HP:0000767
7 osteopenia 32 HP:0000938
8 seizures 32 HP:0001250
9 failure to thrive 32 HP:0001508
10 gingival overgrowth 32 HP:0000212
11 macrotia 32 HP:0000400
12 abnormality of the dentition 32 HP:0000164
13 pes planus 32 HP:0001763
14 microcephaly 32 HP:0000252
15 sensorineural hearing impairment 32 HP:0000407
16 thick eyebrow 32 HP:0000574
17 short stature 32 HP:0004322
18 hypertonia 32 HP:0001276
19 stereotypy 32 HP:0000733
20 brachycephaly 32 HP:0000248
21 retrognathia 32 HP:0000278
22 coxa valga 32 HP:0002673
23 everted lower lip vermilion 32 HP:0000232
24 postnatal growth retardation 32 HP:0008897
25 prominent nasal bridge 32 HP:0000426
26 wide mouth 32 HP:0000154
27 aggressive behavior 32 HP:0000718
28 downslanted palpebral fissures 32 HP:0000494
29 open mouth 32 HP:0000194
30 protruding tongue 32 HP:0010808
31 ventricular septal defect 32 HP:0001629
32 thin vermilion border 32 HP:0000233
33 long eyelashes 32 HP:0000527
34 proximal placement of thumb 32 HP:0009623
35 sparse hair 32 occasional (7.5%) HP:0008070
36 generalized hypotonia 32 HP:0001290
37 slender long bone 32 HP:0003100
38 posteriorly rotated ears 32 HP:0000358
39 unsteady gait 32 HP:0002317
40 hirsutism 32 occasional (7.5%) HP:0001007
41 macrodontia 32 HP:0001572
42 self-mutilation 32 HP:0000742
43 type ii transferrin isoform profile 32 HP:0012301
44 abnormal isoelectric focusing of serum transferrin 32 HP:0003160
45 thoracolumbar kyphoscoliosis 32 HP:0003423
46 reduced factor xi activity 32 HP:0001929
47 diastema 32 HP:0000699
48 low hanging columella 32 HP:0009765
49 reduced factor ix activity 32 HP:0011858
50 midfrontal capillary hemangioma 32 HP:0007466

UMLS symptoms related to Congenital Disorder of Glycosylation, Type Iia:


seizures

MGI Mouse Phenotypes related to Congenital Disorder of Glycosylation, Type Iia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.23 ALG2 DPM1 MGAT2 MPI PMM2 SEC23B

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Iia

Search Clinical Trials , NIH Clinical Center for Congenital Disorder of Glycosylation, Type Iia

Genetic Tests for Congenital Disorder of Glycosylation, Type Iia

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

# Genetic test Affiliating Genes
1 Carbohydrate-Deficient Glycoprotein Syndrome Type Ii 29 MGAT2

Anatomical Context for Congenital Disorder of Glycosylation, Type Iia

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

41
Bone, Skin, Liver, Eye, Tongue, Brain

Publications for Congenital Disorder of Glycosylation, Type Iia

Articles related to Congenital Disorder of Glycosylation, Type Iia:

# Title Authors Year
1
Mice with a homozygous deletion of the Mgat2 gene encoding UDP-N-acetylglucosamine:alpha-6-D-mannoside beta1,2-N-acetylglucosaminyltransferase II: a model for congenital disorder of glycosylation type IIa. ( 12417412 )
2002
2
Modeling human congenital disorder of glycosylation type IIa in the mouse: conservation of asparagine-linked glycan-dependent functions in mammalian physiology and insights into disease pathogenesis. ( 11805078 )
2001

Variations for Congenital Disorder of Glycosylation, Type Iia

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

75
# Symbol AA change Variation ID SNP ID
1 MGAT2 p.His262Arg VAR_003415 rs104894447
2 MGAT2 p.Ser290Phe VAR_003416 rs104894446
3 MGAT2 p.Asn318Asp VAR_012343 rs104894448

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

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 MGAT2 NM_002408.3(MGAT2): c.869C> T (p.Ser290Phe) single nucleotide variant Pathogenic rs104894446 GRCh37 Chromosome 14, 50088855: 50088855
2 MGAT2 NM_002408.3(MGAT2): c.869C> T (p.Ser290Phe) single nucleotide variant Pathogenic rs104894446 GRCh38 Chromosome 14, 49622137: 49622137
3 MGAT2 NM_002408.3(MGAT2): c.785A> G (p.His262Arg) single nucleotide variant Pathogenic rs104894447 GRCh37 Chromosome 14, 50088771: 50088771
4 MGAT2 NM_002408.3(MGAT2): c.785A> G (p.His262Arg) single nucleotide variant Pathogenic rs104894447 GRCh38 Chromosome 14, 49622053: 49622053
5 MGAT2 NM_002408.3(MGAT2): c.952A> G (p.Asn318Asp) single nucleotide variant Pathogenic rs104894448 GRCh37 Chromosome 14, 50088938: 50088938
6 MGAT2 NM_002408.3(MGAT2): c.952A> G (p.Asn318Asp) single nucleotide variant Pathogenic rs104894448 GRCh38 Chromosome 14, 49622220: 49622220
7 MGAT2 NM_002408.3(MGAT2): c.1017T> A (p.Cys339Ter) single nucleotide variant Pathogenic rs104894449 GRCh37 Chromosome 14, 50089003: 50089003
8 MGAT2 NM_002408.3(MGAT2): c.1017T> A (p.Cys339Ter) single nucleotide variant Pathogenic rs104894449 GRCh38 Chromosome 14, 49622285: 49622285
9 MGAT2 NM_002408.3(MGAT2): c.711G> C (p.Lys237Asn) single nucleotide variant Pathogenic/Likely pathogenic rs730882218 GRCh38 Chromosome 14, 49621979: 49621979
10 MGAT2 NM_002408.3(MGAT2): c.711G> C (p.Lys237Asn) single nucleotide variant Pathogenic/Likely pathogenic rs730882218 GRCh37 Chromosome 14, 50088697: 50088697
11 DNAAF2; MGAT2 NM_002408.3(MGAT2): c.261G> T (p.Leu87=) single nucleotide variant Benign/Likely benign rs2228449 GRCh37 Chromosome 14, 50088247: 50088247
12 DNAAF2; MGAT2 NM_002408.3(MGAT2): c.261G> T (p.Leu87=) single nucleotide variant Benign/Likely benign rs2228449 GRCh38 Chromosome 14, 49621529: 49621529
13 MGAT2 NM_002408.3(MGAT2): c.768T> G (p.Leu256=) single nucleotide variant Benign rs77872234 GRCh37 Chromosome 14, 50088754: 50088754
14 MGAT2 NM_002408.3(MGAT2): c.768T> G (p.Leu256=) single nucleotide variant Benign rs77872234 GRCh38 Chromosome 14, 49622036: 49622036
15 MGAT2 NM_002408.3(MGAT2): c.688A> C (p.Thr230Pro) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 49621956: 49621956
16 MGAT2 NM_002408.3(MGAT2): c.688A> C (p.Thr230Pro) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 50088674: 50088674
17 MGAT2 NM_002408.3(MGAT2): c.862G> A (p.Val288Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 50088848: 50088848
18 MGAT2 NM_002408.3(MGAT2): c.862G> A (p.Val288Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 49622130: 49622130
19 MGAT2 NM_002408.3(MGAT2): c.232G> A (p.Ala78Thr) single nucleotide variant Uncertain significance rs138365004 GRCh38 Chromosome 14, 49621500: 49621500
20 MGAT2 NM_002408.3(MGAT2): c.232G> A (p.Ala78Thr) single nucleotide variant Uncertain significance rs138365004 GRCh37 Chromosome 14, 50088218: 50088218

Expression for Congenital Disorder of Glycosylation, Type Iia

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

Pathways for Congenital Disorder of Glycosylation, Type Iia

Pathways related to Congenital Disorder of Glycosylation, Type Iia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.16 ALG2 DPM1 MGAT2 MPDU1 MPI PMM2
2
Show member pathways
12.32 ALG2 DPM1 MGAT2 MPDU1 MPI PMM2
3
Show member pathways
11.31 ALG2 DPM1 MPDU1 MPI PMM2
4
Show member pathways
11.25 MPI PMM2
5
Show member pathways
11.12 ALG2 DPM1 MGAT2
6
Show member pathways
10.99 MPI PMM2

GO Terms for Congenital Disorder of Glycosylation, Type Iia

Cellular components related to Congenital Disorder of Glycosylation, Type Iia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 8.92 ALG2 DPM1 MPDU1 SEC23B

Biological processes related to Congenital Disorder of Glycosylation, Type Iia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein N-linked glycosylation GO:0006487 9.37 MGAT2 PMM2
2 mannosylation GO:0097502 9.32 ALG2 DPM1
3 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.26 ALG2 MPDU1
4 oligosaccharide biosynthetic process GO:0009312 9.16 MGAT2 MPDU1
5 protein glycosylation GO:0006486 9.02 ALG2 DPM1 MGAT2 MPI PMM2
6 GDP-mannose biosynthetic process GO:0009298 8.96 MPI PMM2

Molecular functions related to Congenital Disorder of Glycosylation, Type Iia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring glycosyl groups GO:0016757 8.8 ALG2 DPM1 MGAT2

Sources for Congenital Disorder of Glycosylation, Type Iia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....