MDDGA12
MCID: MSC102
MIFTS: 29

Muscular Dystrophy-Dystroglycanopathy , Type a, 12 (MDDGA12)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

MalaCards integrated aliases for Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

Name: Muscular Dystrophy-Dystroglycanopathy , Type a, 12 57 72 29 13 6 70
Mddga12 57 72
Muscular Dystrophy-Dystroglycanopathy Congenital with Brain and Eye Anomalies A12 72
Walker-Warburg Syndrome or Muscle-Eye-Brain Disease, Pomk-Related 57
Walker-Warburg Syndrome or Muscle-Eye-Brain Disease Pomk-Related 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
clinical variability
three unrelated families have been reported (last curated november 2014)


HPO:

31
muscular dystrophy-dystroglycanopathy , type a, 12:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

OMIM® : 57 Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Stevens et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670). (615249) (Updated 20-May-2021)

MalaCards based summary : Muscular Dystrophy-Dystroglycanopathy , Type a, 12, also known as mddga12, is related to congenital muscular dystrophy-dystroglycanopathy type a12. An important gene associated with Muscular Dystrophy-Dystroglycanopathy , Type a, 12 is POMK (Protein O-Mannose Kinase). Affiliated tissues include eye and brain, and related phenotypes are agenesis of corpus callosum and hydrocephalus

UniProtKB/Swiss-Prot : 72 Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A12: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle- eye-brain disease.

Related Diseases for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Diseases in the Muscular Dystrophy-Dystroglycanopathy family:

Muscular Dystrophy-Dystroglycanopathy , Type a, 1 Muscular Dystrophy-Dystroglycanopathy , Type a, 3
Muscular Dystrophy-Dystroglycanopathy , Type a, 4 Muscular Dystrophy-Dystroglycanopathy , Type B, 5
Muscular Dystrophy-Dystroglycanopathy , Type C, 5 Muscular Dystrophy-Dystroglycanopathy , Type B, 6
Muscular Dystrophy-Dystroglycanopathy , Type C, 1 Muscular Dystrophy-Dystroglycanopathy , Type C, 4
Muscular Dystrophy-Dystroglycanopathy , Type C, 15 Muscular Dystrophy-Dystroglycanopathy , Type a, 2
Muscular Dystrophy-Dystroglycanopathy , Type B, 3 Muscular Dystrophy-Dystroglycanopathy , Type B, 4
Muscular Dystrophy-Dystroglycanopathy , Type a, 5 Muscular Dystrophy-Dystroglycanopathy , Type a, 6
Muscular Dystrophy-Dystroglycanopathy , Type B, 1 Muscular Dystrophy-Dystroglycanopathy , Type B, 2
Muscular Dystrophy-Dystroglycanopathy , Type C, 3 Muscular Dystrophy-Dystroglycanopathy , Type C, 2
Muscular Dystrophy-Dystroglycanopathy , Type C, 9 Muscular Dystrophy-Dystroglycanopathy , Type a, 7
Muscular Dystrophy-Dystroglycanopathy , Type a, 8 Muscular Dystrophy-Dystroglycanopathy , Type a, 10
Muscular Dystrophy-Dystroglycanopathy , Type a, 11 Muscular Dystrophy-Dystroglycanopathy , Type a, 12
Muscular Dystrophy-Dystroglycanopathy , Type a, 13 Muscular Dystrophy-Dystroglycanopathy , Type a, 14
Muscular Dystrophy-Dystroglycanopathy , Type B, 14 Muscular Dystrophy-Dystroglycanopathy , Type C, 14
Muscular Dystrophy-Dystroglycanopathy , Type C, 7 Muscular Dystrophy-Dystroglycanopathy , Type C, 12
Muscular Dystrophy-Dystroglycanopathy , Type a, 9 Muscular Dystrophy-Dystroglycanopathy , Type C, 8
Muscular Dystrophy-Dystroglycanopathy , Type B, 15 Congenital Muscular Dystrophy-Dystroglycanopathy Type a
Congenital Muscular Dystrophy-Dystroglycanopathy Type A11 Congenital Muscular Dystrophy-Dystroglycanopathy Type A8
Congenital Muscular Dystrophy-Dystroglycanopathy Type A9 Congenital Muscular Dystrophy-Dystroglycanopathy A14
Congenital Muscular Dystrophy-Dystroglycanopathy A7 Congenital Muscular Dystrophy-Dystroglycanopathy Type A12
Congenital Muscular Dystrophy-Dystroglycanopathy Type A3 Congenital Muscular Dystrophy-Dystroglycanopathy Type A1
Congenital Muscular Dystrophy-Dystroglycanopathy Type A13 Congenital Muscular Dystrophy-Dystroglycanopathy Type A10
Congenital Muscular Dystrophy-Dystroglycanopathy Type A2 Congenital Muscular Dystrophy-Dystroglycanopathy Type A5
Congenital Muscular Dystrophy-Dystroglycanopathy Type A6

Diseases related to Muscular Dystrophy-Dystroglycanopathy , Type a, 12 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 congenital muscular dystrophy-dystroglycanopathy type a12 11.0

Symptoms & Phenotypes for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Human phenotypes related to Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 31 occasional (7.5%) HP:0001274
2 hydrocephalus 31 occasional (7.5%) HP:0000238
3 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
4 cerebellar hypoplasia 31 occasional (7.5%) HP:0001321
5 type ii lissencephaly 31 occasional (7.5%) HP:0007260
6 hypoplasia of the brainstem 31 occasional (7.5%) HP:0002365
7 seizure 31 occasional (7.5%) HP:0001250
8 agyria 31 very rare (1%) HP:0031882
9 scoliosis 31 HP:0002650
10 cataract 31 HP:0000518
11 global developmental delay 31 HP:0001263
12 neonatal hypotonia 31 HP:0001319
13 flexion contracture 31 HP:0001371
14 elevated serum creatine kinase 31 HP:0003236
15 respiratory insufficiency due to muscle weakness 31 HP:0002747
16 microphthalmia 31 HP:0000568
17 reduced visual acuity 31 HP:0007663
18 poor head control 31 HP:0002421
19 feeding difficulties 31 HP:0011968
20 muscular dystrophy 31 HP:0003560
21 psychomotor retardation 31 HP:0025356
22 retinal degeneration 31 HP:0000546
23 coloboma 31 HP:0000589
24 poor speech 31 HP:0002465
25 abnormally large globe 31 HP:0001090
26 progressive microcephaly 31 HP:0000253

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
scoliosis

Head And Neck Eyes:
cataract
microphthalmia
retinal degeneration
coloboma
decreased visual acuity
more
Respiratory:
respiratory insufficiency due to muscle weakness

Head And Neck Ears:
sensorineural hearing loss

Abdomen Gastrointestinal:
feeding problems

Neurologic Central Nervous System:
hydrocephalus
cerebellar hypoplasia
poor speech
psychomotor retardation, severe
delayed psychomotor development, severe
more
Muscle Soft Tissue:
neonatal hypotonia
muscular dystrophy
muscle weakness and atrophy, progressive
defective glycosylation of alpha-dystroglycan seen on biopsy
secondary loss of merosin and desmin

Head And Neck Head:
poor head control
microcephaly, progressive (1 patient)

Skeletal:
joint contractures

Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM®:

615249 (Updated 20-May-2021)

Drugs & Therapeutics for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Search Clinical Trials , NIH Clinical Center for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Genetic Tests for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Genetic tests related to Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

# Genetic test Affiliating Genes
1 Muscular Dystrophy-Dystroglycanopathy (congenital with Brain and Eye Anomalies), Type a, 12 29 POMK

Anatomical Context for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

MalaCards organs/tissues related to Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

40
Eye, Brain

Publications for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Articles related to Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

# Title Authors PMID Year
1
POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations. 57 6
24925318 2014
2
POMK mutation in a family with congenital muscular dystrophy with merosin deficiency, hypomyelination, mild hearing deficit and intellectual disability. 6 57
24556084 2014
3
Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry. 6 57
23519211 2013
4
Mutations in B3GALNT2 cause congenital muscular dystrophy and hypoglycosylation of α-dystroglycan. 57
23453667 2013
5
Pathogenic homozygous variant in POMK gene is the cause of prenatally detected severe ventriculomegaly in two Lithuanian families. 61
31833209 2020

Variations for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

ClinVar genetic disease variations for Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

6 (show top 50) (show all 94)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POMK NM_032237.5(POMK):c.410T>G (p.Leu137Arg) SNV Pathogenic 50610 rs397509385 GRCh37: 8:42977377-42977377
GRCh38: 8:43122234-43122234
2 POMK NM_032237.5(POMK):c.773A>G (p.Gln258Arg) SNV Pathogenic 50611 rs397509386 GRCh37: 8:42977740-42977740
GRCh38: 8:43122597-43122597
3 POMK NM_032237.5(POMK):c.325C>T (p.Gln109Ter) SNV Pathogenic 133346 rs587777423 GRCh37: 8:42977292-42977292
GRCh38: 8:43122149-43122149
4 POMK NM_032237.5(POMK):c.288del (p.Leu97fs) Deletion Pathogenic 160348 rs606231306 GRCh37: 8:42977253-42977253
GRCh38: 8:43122110-43122110
5 POMK NM_032237.5(POMK):c.905T>A (p.Val302Asp) SNV Pathogenic 160349 rs199756983 GRCh37: 8:42977872-42977872
GRCh38: 8:43122729-43122729
6 POMK NM_032237.5(POMK):c.238_239del (p.Glu80fs) Deletion Pathogenic 582702 rs1454006905 GRCh37: 8:42958928-42958929
GRCh38: 8:43103785-43103786
7 POMK NM_032237.5(POMK):c.43dup (p.Arg15fs) Duplication Pathogenic 817678 rs749980792 GRCh37: 8:42958728-42958729
GRCh38: 8:43103585-43103586
8 POMK NC_000008.11:g.(?_43103539)_(43103840_?)del Deletion Pathogenic 651249 GRCh37: 8:42958682-42958983
GRCh38: 8:43103539-43103840
9 POMK NM_032237.5(POMK):c.10C>T (p.Gln4Ter) SNV Pathogenic 849427 GRCh37: 8:42958701-42958701
GRCh38: 8:43103558-43103558
10 POMK NM_032237.5(POMK):c.47A>G (p.Glu16Gly) SNV Uncertain significance 851474 GRCh37: 8:42958738-42958738
GRCh38: 8:43103595-43103595
11 POMK NM_032237.5(POMK):c.457C>T (p.Pro153Ser) SNV Uncertain significance 857754 GRCh37: 8:42977424-42977424
GRCh38: 8:43122281-43122281
12 POMK NM_032237.5(POMK):c.833A>G (p.Glu278Gly) SNV Uncertain significance 860305 GRCh37: 8:42977800-42977800
GRCh38: 8:43122657-43122657
13 POMK NM_032237.5(POMK):c.773A>G (p.Gln258Arg) SNV Uncertain significance 50611 rs397509386 GRCh37: 8:42977740-42977740
GRCh38: 8:43122597-43122597
14 POMK NM_032237.5(POMK):c.168C>G (p.Pro56=) SNV Uncertain significance 863624 GRCh37: 8:42958859-42958859
GRCh38: 8:43103716-43103716
15 POMK NM_032237.5(POMK):c.619G>A (p.Asp207Asn) SNV Uncertain significance 863774 GRCh37: 8:42977586-42977586
GRCh38: 8:43122443-43122443
16 overlap with 6 genes NC_000008.10:g.(?_42693095)_(42978030_?)dup Duplication Uncertain significance 653514 GRCh37: 8:42693095-42978030
GRCh38: 8:42837952-43122887
17 POMK NM_032237.5(POMK):c.76A>C (p.Ile26Leu) SNV Uncertain significance 661426 rs1586671643 GRCh37: 8:42958767-42958767
GRCh38: 8:43103624-43103624
18 POMK NM_032237.5(POMK):c.271G>A (p.Ala91Thr) SNV Uncertain significance 665426 rs1365587547 GRCh37: 8:42958962-42958962
GRCh38: 8:43103819-43103819
19 POMK NM_032237.5(POMK):c.265G>A (p.Glu89Lys) SNV Uncertain significance 838680 GRCh37: 8:42958956-42958956
GRCh38: 8:43103813-43103813
20 POMK NM_032237.5(POMK):c.719T>C (p.Met240Thr) SNV Uncertain significance 841233 GRCh37: 8:42977686-42977686
GRCh38: 8:43122543-43122543
21 POMK NM_032237.5(POMK):c.620A>G (p.Asp207Gly) SNV Uncertain significance 843307 GRCh37: 8:42977587-42977587
GRCh38: 8:43122444-43122444
22 POMK NM_032237.5(POMK):c.599G>T (p.Arg200Leu) SNV Uncertain significance 845543 GRCh37: 8:42977566-42977566
GRCh38: 8:43122423-43122423
23 POMK NM_032237.5(POMK):c.979G>C (p.Val327Leu) SNV Uncertain significance 940329 GRCh37: 8:42977946-42977946
GRCh38: 8:43122803-43122803
24 POMK NM_032237.5(POMK):c.701T>C (p.Val234Ala) SNV Uncertain significance 944279 GRCh37: 8:42977668-42977668
GRCh38: 8:43122525-43122525
25 POMK NM_032237.5(POMK):c.859G>C (p.Asp287His) SNV Uncertain significance 944706 GRCh37: 8:42977826-42977826
GRCh38: 8:43122683-43122683
26 POMK NM_032237.5(POMK):c.874C>T (p.Leu292Phe) SNV Uncertain significance 947914 GRCh37: 8:42977841-42977841
GRCh38: 8:43122698-43122698
27 POMK NM_032237.5(POMK):c.657C>A (p.Ser219Arg) SNV Uncertain significance 949145 GRCh37: 8:42977624-42977624
GRCh38: 8:43122481-43122481
28 POMK NM_032237.5(POMK):c.282+1G>C SNV Uncertain significance 949777 GRCh37: 8:42958974-42958974
GRCh38: 8:43103831-43103831
29 POMK NM_032237.5(POMK):c.827A>G (p.Tyr276Cys) SNV Uncertain significance 957806 GRCh37: 8:42977794-42977794
GRCh38: 8:43122651-43122651
30 POMK NM_032237.5(POMK):c.55C>T (p.Pro19Ser) SNV Uncertain significance 966592 GRCh37: 8:42958746-42958746
GRCh38: 8:43103603-43103603
31 POMK NM_032237.5(POMK):c.926T>C (p.Ile309Thr) SNV Uncertain significance 969132 GRCh37: 8:42977893-42977893
GRCh38: 8:43122750-43122750
32 POMK NM_032237.5(POMK):c.908G>A (p.Arg303Gln) SNV Uncertain significance 971161 GRCh37: 8:42977875-42977875
GRCh38: 8:43122732-43122732
33 POMK NM_032237.5(POMK):c.454_459delinsAACCC (p.His152fs) Indel Uncertain significance 971200 GRCh37: 8:42977421-42977426
GRCh38: 8:43122278-43122283
34 POMK NM_032237.5(POMK):c.661T>C (p.Phe221Leu) SNV Uncertain significance 971345 GRCh37: 8:42977628-42977628
GRCh38: 8:43122485-43122485
35 POMK NM_032237.5(POMK):c.334A>G (p.Ser112Gly) SNV Uncertain significance 971481 GRCh37: 8:42977301-42977301
GRCh38: 8:43122158-43122158
36 POMK NM_032237.5(POMK):c.1A>G (p.Met1Val) SNV Uncertain significance 999804 GRCh37: 8:42958692-42958692
GRCh38: 8:43103549-43103549
37 POMK NM_032237.5(POMK):c.121T>G (p.Phe41Val) SNV Uncertain significance 1006660 GRCh37: 8:42958812-42958812
GRCh38: 8:43103669-43103669
38 POMK NM_032237.5(POMK):c.545C>T (p.Ala182Val) SNV Uncertain significance 1009080 GRCh37: 8:42977512-42977512
GRCh38: 8:43122369-43122369
39 POMK NM_032237.5(POMK):c.28A>G (p.Arg10Gly) SNV Uncertain significance 1009402 GRCh37: 8:42958719-42958719
GRCh38: 8:43103576-43103576
40 POMK NM_032237.5(POMK):c.170A>G (p.Tyr57Cys) SNV Uncertain significance 1011886 GRCh37: 8:42958861-42958861
GRCh38: 8:43103718-43103718
41 POMK NM_032237.5(POMK):c.436A>T (p.Thr146Ser) SNV Uncertain significance 1018293 GRCh37: 8:42977403-42977403
GRCh38: 8:43122260-43122260
42 POMK NM_032237.5(POMK):c.74T>C (p.Leu25Pro) SNV Uncertain significance 1021068 GRCh37: 8:42958765-42958765
GRCh38: 8:43103622-43103622
43 POMK NM_032237.5(POMK):c.326A>G (p.Gln109Arg) SNV Uncertain significance 1021659 GRCh37: 8:42977293-42977293
GRCh38: 8:43122150-43122150
44 POMK NM_032237.5(POMK):c.663C>A (p.Phe221Leu) SNV Uncertain significance 1023219 GRCh37: 8:42977630-42977630
GRCh38: 8:43122487-43122487
45 POMK NM_032237.5(POMK):c.44G>A (p.Arg15Gln) SNV Uncertain significance 705716 rs377725187 GRCh37: 8:42958735-42958735
GRCh38: 8:43103592-43103592
46 POMK NM_032237.5(POMK):c.565A>G (p.Ile189Val) SNV Uncertain significance 436700 rs149297443 GRCh37: 8:42977532-42977532
GRCh38: 8:43122389-43122389
47 POMK NM_032237.5(POMK):c.82G>T (p.Ala28Ser) SNV Uncertain significance 1041532 GRCh37: 8:42958773-42958773
GRCh38: 8:43103630-43103630
48 POMK NM_032237.5(POMK):c.796G>A (p.Val266Met) SNV Uncertain significance 1045451 GRCh37: 8:42977763-42977763
GRCh38: 8:43122620-43122620
49 POMK NM_032237.5(POMK):c.3G>C (p.Met1Ile) SNV Uncertain significance 1047054 GRCh37: 8:42958694-42958694
GRCh38: 8:43103551-43103551
50 POMK NM_032237.5(POMK):c.704A>G (p.Asn235Ser) SNV Uncertain significance 474196 rs200742772 GRCh37: 8:42977671-42977671
GRCh38: 8:43122528-43122528

UniProtKB/Swiss-Prot genetic disease variations for Muscular Dystrophy-Dystroglycanopathy , Type a, 12:

72
# Symbol AA change Variation ID SNP ID
1 POMK p.Leu137Arg VAR_069625 rs397509385
2 POMK p.Gln258Arg VAR_069626 rs397509386
3 POMK p.Val302Asp VAR_072560 rs199756983

Expression for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Search GEO for disease gene expression data for Muscular Dystrophy-Dystroglycanopathy , Type a, 12.

Pathways for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

GO Terms for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

Sources for Muscular Dystrophy-Dystroglycanopathy , Type a, 12

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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