MLC2A
MCID: MGL010
MIFTS: 40

Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a (MLC2A)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

MalaCards integrated aliases for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

Name: Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a 56 12 29 13 6 15 71
Mlc2a 56 73
Leukoencephalopathy, Megalencephalic, with Subcortical Cysts, Type 2a 39
Leukoencephalopathy, Megalencephalic, with Subcortical Cysts, 2a 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
brainstem, cerebellum, internal and external capsule, inner rim of the corpus callosum may show disease involvement on mri
onset of macrocephaly in the first year of life
most patients become wheelchair-bound in later childhood


HPO:

31
megalencephalic leukoencephalopathy with subcortical cysts 2a:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:



Summaries for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

OMIM : 56 Megalencephalic leukoencephalopathy with subcortical cysts-2A is an autosomal recessive neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. Brain MRI shows typical white matter abnormalities, including swelling of the cerebral white matter and subcortical cysts, in all stages of the disease (summary by Lopez-Hernandez et al., 2011). Heterozygous mutations in the HEPACAM gene can cause a similar, but less severe disorder that shows improvement of MRI changes with age (MLC2B; 613926). (613925)

MalaCards based summary : Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a, also known as mlc2a, is related to megalencephalic leukoencephalopathy with subcortical cysts 2b, remitting, with or without mental retardation and down syndrome, and has symptoms including seizures, ataxia and muscle spasticity. An important gene associated with Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a is HEPACAM (Hepatic And Glial Cell Adhesion Molecule), and among its related pathways/superpathways is Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways. Affiliated tissues include brain, heart and cerebellum, and related phenotypes are intellectual disability and macrocephaly

Disease Ontology : 12 A megalencephalic leukoencephalopathy with subcortical cysts characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, cognitive decline of variable severity, white matter abnormalities, including swelling of the cerebral white matter and subcortical cysts that has material basis in homozygous or compound heterozygous mutation in HEPACAM on chromosome 11q24.

UniProtKB/Swiss-Prot : 73 Leukoencephalopathy, megalencephalic, with subcortical cysts, 2A: A neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. The brain appears swollen on magnetic resonance imaging with white-matter abnormalities and subcortical cysts, in all stages of the disease.

Related Diseases for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Graphical network of the top 20 diseases related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:



Diseases related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Symptoms & Phenotypes for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Human phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 macrocephaly 31 HP:0000256
3 spasticity 31 HP:0001257
4 ataxia 31 HP:0001251
5 motor delay 31 HP:0001270
6 dysarthria 31 HP:0001260
7 ventriculomegaly 31 HP:0002119
8 cerebellar atrophy 31 HP:0001272
9 cerebral atrophy 31 HP:0002059
10 progressive neurologic deterioration 31 HP:0002344
11 megalencephaly 31 HP:0001355
12 diffuse white matter abnormalities 31 HP:0007204
13 seizure 31 HP:0001250
14 diffuse swelling of cerebral white matter 31 HP:0007341

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly

Neurologic Central Nervous System:
seizures
hypertonia
spasticity
ataxia
dysarthria
more

Clinical features from OMIM:

613925

UMLS symptoms related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:


seizures, ataxia, muscle spasticity

GenomeRNAi Phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-10 9.4 TUBB4A
2 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.4 MECP2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-135 9.4 MECP2 TUBB4A
4 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.4 TUBB4A
5 Increased shRNA abundance (Z-score > 2) GR00366-A-200 9.4 MECP2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.4 MECP2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-26 9.4 MECP2 TUBB4A
8 Increased shRNA abundance (Z-score > 2) GR00366-A-27 9.4 MECP2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.4 MECP2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.4 MECP2

MGI Mouse Phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.7 GRIK4 HEPACAM HIP1 HSPD1 HSPG2 MECP2
2 muscle MP:0005369 9.63 HIP1 HSPD1 HSPG2 PLP1 ROBO4 SORL1
3 respiratory system MP:0005388 9.17 HIP1 HSPD1 HSPG2 MECP2 PKNOX2 ROBO3

Drugs & Therapeutics for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Search Clinical Trials , NIH Clinical Center for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Genetic Tests for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Genetic tests related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

# Genetic test Affiliating Genes
1 Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a 29 HEPACAM

Anatomical Context for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

MalaCards organs/tissues related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

40
Brain, Heart, Cerebellum, Temporal Lobe, Smooth Muscle, Cardiac Myocytes

Publications for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Articles related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

(show top 50) (show all 66)
# Title Authors PMID Year
1
Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. 56 6
21419380 2011
2
Megalencephalic Leukoencephalopathy with Subcortical Cysts 61 6
20301707 2003
3
Megalencephalic leukoencephalopathy with cysts without MLC1 defect. 56
20517947 2010
4
Efficient differentiation of human pluripotent stem cells into cardiomyocytes on cell sorting thermoresponsive surface. 61
32450407 2020
5
Structural basis for the dominant or recessive character of GLIALCAM mutations found in leukodystrophies. 61
31960914 2020
6
Identification in Chinese patients with GLIALCAM mutations of megalencephalic leukoencephalopathy with subcortical cysts and brain pathological study on Glialcam knock-in mouse models. 61
31372844 2019
7
Second harmonic generation microscopy of early embryonic mouse hearts. 61
31259060 2019
8
Priming with oxytocin and relaxin improves cardiac differentiation of adipose tissue-derived stem cells. 61
30362159 2019
9
Comparative Proteomic Analysis Reveals the Upregulation of Ketogenesis in Cardiomyocytes Differentiated from Induced Pluripotent Stem Cells. 61
30724459 2019
10
Maturation of three-dimensional, hiPSC-derived cardiomyocyte spheroids utilizing cyclic, uniaxial stretch and electrical stimulation. 61
31276558 2019
11
Commonly used thiol-containing antioxidants reduce cardiac differentiation and alter gene expression ratios of sarcomeric isoforms. 61
29920245 2018
12
Expression profile of long non-coding RNAs during the differentiation of human umbilical cord derived mesenchymal stem cells into cardiomyocyte-like cells. 61
29633064 2018
13
Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants. 61
29661901 2018
14
Cardiotrophic Growth Factor-Driven Induction of Human Muse Cells Into Cardiomyocyte-Like Phenotype. 61
29637816 2018
15
Deletion of Cdc42 in embryonic cardiomyocytes results in right ventricle hypoplasia. 61
29101495 2017
16
Functional expression and pharmaceutical efficacy of cardiac-specific ion channels in human embryonic stem cell-derived cardiomyocytes. 61
29062050 2017
17
Impaired redox environment modulates cardiogenic and ion-channel gene expression in cardiac-resident and non-resident mesenchymal stem cells. 61
28092181 2017
18
Sphingosine 1-phosphate receptor-1 in cardiomyocytes is required for normal cardiac development. 61
27333774 2016
19
Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.). 61
26246399 2016
20
Three-dimensional poly-(ε-caprolactone) nanofibrous scaffolds directly promote the cardiomyocyte differentiation of murine-induced pluripotent stem cells through Wnt/β-catenin signaling. 61
26335746 2015
21
Stimulation of cardiomyogenesis from mouse embryonic stem cells by nuclear translocation of cardiotrophin-1. 61
26005169 2015
22
Isolation of contractile cardiomyocytes from human pluripotent stem-cell-derived cardiomyogenic cultures using a human NCX1-EGFP reporter. 61
25075536 2015
23
Cardiogenesis of embryonic stem cells with liquid marble micro-bioreactor. 61
24818841 2015
24
Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics. 61
26340748 2015
25
Atrial and ventricular specification of ADSCs is stimulated by different doses of BMP4. 61
25216643 2014
26
High efficiency differentiation of human pluripotent stem cells to cardiomyocytes and characterization by flow cytometry. 61
25286293 2014
27
Expanding the spectrum of megalencephalic leukoencephalopathy with subcortical cysts in two patients with GLIALCAM mutations. 61
24202401 2014
28
[Morphological and molecular bases of cardiac development]. 61
24088538 2013
29
Static magnetic fields increase cardiomyocyte differentiation of Flk-1+ cells derived from mouse embryonic stem cells via Ca2+ influx and ROS production. 61
22465345 2013
30
Atrial identity is determined by a COUP-TFII regulatory network. 61
23725765 2013
31
Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture. 61
23400258 2013
32
Functional vascular smooth muscle-like cells derived from adult mouse uterine mesothelial cells. 61
23405120 2013
33
Primitive cardiac cells from human embryonic stem cells. 61
21933026 2012
34
Polycomb repressive complex 2 regulates normal development of the mouse heart. 61
22158708 2012
35
Deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction. 61
21242479 2011
36
SDF-1-enhanced cardiogenesis requires CXCR4 induction in pluripotent stem cells. 61
20842469 2010
37
Cardiomyocyte sulfonylurea receptor 2-KATP channel mediates cardioprotection and ST segment elevation. 61
20656890 2010
38
The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells. 61
19945747 2010
39
iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. 61
19696409 2009
40
Migration and differentiation of human umbilical cord stem cells after heart injury in chicken embryos. 61
18393637 2009
41
Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium. 61
18503051 2008
42
Induction by left ventricular overload and left ventricular failure of the human Jumonji gene (JARID2) encoding a protein that regulates transcription and reexpression of a protective fetal program. 61
18805276 2008
43
Generation of functional murine cardiac myocytes from induced pluripotent stem cells. 61
18625890 2008
44
Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice. 61
18448675 2008
45
Epicardium-derived cells in development of annulus fibrosis and persistence of accessory pathways. 61
18332266 2008
46
Peroxisome proliferator-activated receptor alpha agonists enhance cardiomyogenesis of mouse ES cells by utilization of a reactive oxygen species-dependent mechanism. 61
17951219 2008
47
Distinct roles of Wnt/beta-catenin and Bmp signaling during early cardiogenesis. 61
18000065 2007
48
Vascular remodeling of the mouse yolk sac requires hemodynamic force. 61
17720695 2007
49
Activation of MEK-ERK by heregulin-beta1 promotes the development of cardiomyocytes derived from ES cells. 61
17678625 2007
50
Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase. 61
17298980 2007

Variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

ClinVar genetic disease variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HEPACAM NM_152722.5(HEPACAM):c.587C>A (p.Ser196Tyr)SNV Pathogenic 30914 rs387907049 11:124793747-124793747 11:124923851-124923851
2 HEPACAM HEPACAM, TRP263TERundetermined variant Pathogenic 30915
3 HEPACAM NM_152722.5(HEPACAM):c.275G>A (p.Arg92Gln)SNV Pathogenic 30916 rs387907050 11:124794776-124794776 11:124924880-124924880
4 HEPACAM NM_152722.5(HEPACAM):c.631G>A (p.Asp211Asn)SNV Pathogenic 30917 rs387907051 11:124793703-124793703 11:124923807-124923807
5 HEPACAM NM_152722.5(HEPACAM):c.292C>T (p.Arg98Cys)SNV Pathogenic 30918 rs387907052 11:124794759-124794759 11:124924863-124924863
6 HEPACAM NM_152722.5(HEPACAM):c.265G>A (p.Gly89Ser)SNV Pathogenic 30919 rs387907053 11:124794786-124794786 11:124924890-124924890
7 HEPACAM NM_152722.5(HEPACAM):c.274C>T (p.Arg92Trp)SNV Pathogenic 30921 rs387907055 11:124794777-124794777 11:124924881-124924881
8 HEPACAM NM_152722.5(HEPACAM):c.442C>T (p.Pro148Ser)SNV Likely pathogenic 433199 rs1555055028 11:124793892-124793892 11:124923996-124923996
9 HEPACAM NM_152722.5(HEPACAM):c.614C>T (p.Thr205Ile)SNV Uncertain significance 435410 rs746134081 11:124793720-124793720 11:124923824-124923824
10 HEPACAM NM_152722.5(HEPACAM):c.128T>A (p.Ile43Asn)SNV Uncertain significance 638399 11:124794923-124794923 11:124925027-124925027

UniProtKB/Swiss-Prot genetic disease variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a:

73
# Symbol AA change Variation ID SNP ID
1 HEPACAM p.Leu23His VAR_065849
2 HEPACAM p.Arg92Gln VAR_065852 rs387907050
3 HEPACAM p.Arg98Cys VAR_065854 rs387907052
4 HEPACAM p.Pro148Ser VAR_065857 rs155505502
5 HEPACAM p.Ser196Tyr VAR_065858 rs387907049
6 HEPACAM p.Asp211Asn VAR_065859 rs387907051

Expression for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Search GEO for disease gene expression data for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a.

Pathways for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Pathways related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.01 PLP1 MECP2 HSPD1

GO Terms for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

Cellular components related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 myelin sheath GO:0043209 8.62 TUBB4A PLP1

Biological processes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein maturation GO:0051604 8.96 SORL1 HSPD1
2 dendrite self-avoidance GO:0070593 8.62 ROBO4 ROBO3

Molecular functions related to Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell-cell adhesion mediator activity GO:0098632 8.62 ROBO4 ROBO3

Sources for Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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19 FMA
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30 HMDB
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56 OMIM
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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