LISX1
MCID: LSS036
MIFTS: 45

Lissencephaly, X-Linked, 1 (LISX1)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Lissencephaly, X-Linked, 1

MalaCards integrated aliases for Lissencephaly, X-Linked, 1:

Name: Lissencephaly, X-Linked, 1 56
Lissencephaly, X-Linked 56 29 13 54 6
Xlis 56 52 73
Lissencephaly and Agenesis of Corpus Callosum 56 52
Subcortical Laminal Heterotopia, X-Linked 56 29
X-Linked Lissencephaly 52 71
Double Cortex 73 71
Lisx1 56 73
Lissencephaly Type 1 Due to Doublecortin Gene Mutation 58
Subcortical Band Heterotopia X-Linked 73
Subcortical Laminar Heterotopia 73
Lissencephaly, X-Linked, Type 1 39
X-Linked Lissencephaly Type 1 58
Subcortical Band Heterotopia 71
Lissencephaly, X-Linked 1 73
Lissencephaly X-Linked 52
Lisx 52
Sclh 73
Sbhx 73

Characteristics:

Orphanet epidemiological data:

58
lissencephaly type 1 due to doublecortin gene mutation
Inheritance: X-linked recessive; Age of onset: Adolescent,Childhood,Infancy,Neonatal;

OMIM:

56
Miscellaneous:
incomplete penetrance
onset in infancy
highly variable phenotype in females
somatic or germline mosaicism may occur

Inheritance:
x-linked


HPO:

31
lissencephaly, x-linked, 1:
Clinical modifier death in infancy
Inheritance x-linked inheritance
Onset and clinical course infantile onset incomplete penetrance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM 56 300067
OMIM Phenotypic Series 56 PS607432
ICD10 via Orphanet 33 Q04.3
UMLS via Orphanet 72 C1848199
Orphanet 58 ORPHA2148
UMLS 71 C1848199 C1848201 C2931857

Summaries for Lissencephaly, X-Linked, 1

UniProtKB/Swiss-Prot : 73 Lissencephaly, X-linked 1: A classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.
Subcortical band heterotopia X-linked: SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.

MalaCards based summary : Lissencephaly, X-Linked, 1, also known as lissencephaly, x-linked, is related to band heterotopia and lissencephaly 1, and has symptoms including seizures and ataxia. An important gene associated with Lissencephaly, X-Linked, 1 is DCX (Doublecortin), and among its related pathways/superpathways are Cytoskeletal Signaling and Lissencephaly gene (LIS1) in neuronal migration and development. Affiliated tissues include cortex, brain and testes, and related phenotypes are seizures and intellectual disability, severe

OMIM : 56 Lissencephaly ('smooth brain') results from migrational arrest of cortical neurons short of their normal destination, and can result in profound mental retardation and seizures. In X-linked lissencephaly-1, affected males generally have more a severe phenotype compared to females. DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome (des Portes et al., 1997). There are several X-linked loci that affect neuronal migration, including the Aicardi locus (304050). (300067)

Related Diseases for Lissencephaly, X-Linked, 1

Diseases in the Lissencephaly, X-Linked, 1 family:

Lissencephaly, X-Linked, 2

Diseases related to Lissencephaly, X-Linked, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 84)
# Related Disease Score Top Affiliating Genes
1 band heterotopia 30.1 PAFAH1B1 DCX
2 lissencephaly 1 30.0 PAFAH1B1 DCX
3 neuronal migration disorders 29.8 PAFAH1B1 DCX
4 lissencephaly 29.4 PAFAH1B1 DCX ARX
5 lennox-gastaut syndrome 29.3 DCX ARX
6 miller-dieker lissencephaly syndrome 29.2 PAFAH1B1 DCX ARX
7 west syndrome 28.6 PAFAH1B1 ARX
8 periventricular nodular heterotopia 28.3 PAFAH1B1 DCX ARX
9 lissencephaly, x-linked, 2 12.9
10 ichthyosis, x-linked 12.2
11 x-linked lissencephaly with abnormal genitalia 11.7
12 chromosome xq26.3 duplication syndrome 11.5
13 diarrhea 10.4
14 microcephaly 10.3
15 pafah1b1-associated lissencephaly/subcortical band heterotopia 10.2
16 periventricular nodular heterotopia 1 10.2
17 visual epilepsy 10.2
18 status epilepticus 10.2
19 encephalopathy 10.2
20 seizure disorder 10.2
21 cryptorchidism, unilateral or bilateral 10.1
22 corpus callosum, agenesis of, with abnormal genitalia 10.1
23 alacrima, achalasia, and mental retardation syndrome 10.1
24 corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia 10.1
25 secretory diarrhea 10.1
26 lactose intolerance 10.1
27 fanconi syndrome 10.1
28 megacolon 10.1
29 exocrine pancreatic insufficiency 10.1
30 hypophosphatasia 10.1
31 hypothyroidism 10.1
32 hypogonadism 10.1
33 hyperinsulinism 10.1
34 hypokalemia 10.1
35 hypogonadotropism 10.1
36 hypoglycemia 10.1
37 cerebral atrophy 10.1
38 myoclonus 10.1
39 systemic lupus erythematosus 10.1
40 retinal detachment 10.1
41 multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 10.1
42 tendinopathy 10.1
43 tendinitis 10.1
44 osteomyelitis 10.1
45 frozen shoulder 10.1
46 bursitis 10.1
47 lupus erythematosus 10.1
48 stomatitis 10.1
49 dcx-related disorders 10.1
50 tubulinopathies 10.1

Graphical network of the top 20 diseases related to Lissencephaly, X-Linked, 1:



Diseases related to Lissencephaly, X-Linked, 1

Symptoms & Phenotypes for Lissencephaly, X-Linked, 1

Human phenotypes related to Lissencephaly, X-Linked, 1:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
3 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
4 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
5 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
6 agenesis of corpus callosum 31 HP:0001274
7 nystagmus 31 HP:0000639
8 intellectual disability 31 HP:0001249
9 ataxia 31 HP:0001251
10 spasticity 31 HP:0001257
11 dysarthria 31 HP:0001260
12 postnatal growth retardation 31 HP:0008897
13 motor delay 31 HP:0001270
14 micropenis 31 HP:0000054
15 pachygyria 31 HP:0001302
16 muscular hypotonia of the trunk 31 HP:0008936
17 gray matter heterotopia 31 HP:0002282
18 agyria 31 HP:0031882

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
nystagmus

Neurologic Central Nervous System:
seizures
ataxia
dysarthria
pachygyria
agyria
more

Clinical features from OMIM:

300067

UMLS symptoms related to Lissencephaly, X-Linked, 1:


seizures, ataxia

Drugs & Therapeutics for Lissencephaly, X-Linked, 1

Search Clinical Trials , NIH Clinical Center for Lissencephaly, X-Linked, 1

Genetic Tests for Lissencephaly, X-Linked, 1

Genetic tests related to Lissencephaly, X-Linked, 1:

# Genetic test Affiliating Genes
1 Lissencephaly, X-Linked 29
2 Subcortical Laminal Heterotopia, X-Linked 29

Anatomical Context for Lissencephaly, X-Linked, 1

MalaCards organs/tissues related to Lissencephaly, X-Linked, 1:

40
Cortex, Brain, Testes, Fetal Brain

Publications for Lissencephaly, X-Linked, 1

Articles related to Lissencephaly, X-Linked, 1:

(show top 50) (show all 68)
# Title Authors PMID Year
1
Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. 54 6 56 61
9489700 1998
2
Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders. 61 6 56
12552055 2003
3
A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. 6 56
9489699 1998
4
Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain. 56 61 54
9097958 1997
5
Somatic and germline mosaic mutations in the doublecortin gene are associated with variable phenotypes. 61 56
10915612 2000
6
Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1. 61 6
10441340 1999
7
Differences in the gyral pattern distinguish chromosome 17-linked and X-linked lissencephaly. 61 56
10430413 1999
8
LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. 61 56
9817918 1998
9
Somatic mutations in cerebral cortical malformations. 56
25140959 2014
10
Phenotypic and molecular characterization of a novel DCX deletion and a review of the literature. 56
19673952 2009
11
Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia. 56
19050731 2009
12
Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures. 56
19342486 2009
13
Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder. 56
19098909 2009
14
DCX-Related Disorders 6
20301364 2007
15
RNAi reveals doublecortin is required for radial migration in rat neocortex. 56
14625554 2003
16
Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX. 56
12034802 2002
17
Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene. 6
11468322 2001
18
Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia. 56
11175293 2001
19
Familial neuronal migration disorder: subcortical laminar heterotopia in a mother and pachygyria in the son. 56
9489790 1998
20
Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22. 56
9132485 1997
21
X-linked pachygyria and agenesis of the corpus callosum: evidence for an X chromosome lissencephaly locus. 56
8053659 1994
22
Periventricular heterotopia and epilepsy. 56
8290091 1994
23
Familial band heterotopias simulating tuberous sclerosis. 56
8327150 1993
24
Stages and patterns of centrifugal arrest of diffuse neuronal migration disorders. 56
8335148 1993
25
Causal heterogeneity in isolated lissencephaly. 56
1620349 1992
26
Diffuse cortical dysplasia, or the 'double cortex' syndrome: the clinical and epileptic spectrum in 10 patients. 56
1922811 1991
27
A novel missense mutation of doublecortin: mutation analysis of Korean patients with subcortical band heterotopia. 54 61
16100463 2005
28
Neuronal migration disorders, genetics, and epileptogenesis. 54 61
15921228 2005
29
Genes that regulate neuronal migration in the cerebral cortex. 61 54
10515162 1999
30
Cloning and developmental expression of the murine homolog of doublecortin. 61 54
9837748 1998
31
X-linked malformations of neuronal migration. 61 54
8757001 1996
32
A critical and previously unsuspected role for doublecortin at the neuromuscular junction in mouse and human. 61
25817838 2015
33
Three human ARX mutations cause the lissencephaly-like and mental retardation with epilepsy-like pleiotropic phenotypes in mice. 54
19605412 2009
34
[Epileptogenic brain malformations: radiological and clinical presentation and indications for genetic testing]. 54
18808783 2008
35
Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate. 54
18412232 2008
36
A novel mutation of the ARX gene in a male with nonsyndromic mental retardation. 54
17641262 2007
37
[Genetic and clinical aspects of lissencephaly]. 54
17571022 2007
38
[X-linked lissencephaly with absent corpus callosum and abnormal genitalia: a report of siblings followed from the prenatal period]. 54
17515135 2007
39
Genetic malformations of cortical development. 54
16724181 2006
40
Neurabin II mediates doublecortin-dephosphorylation on actin filaments. 54
16564023 2006
41
Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1). 54
16530423 2006
42
Genotypically defined lissencephalies show distinct pathologies. 61
16215456 2005
43
Doublecortin association with actin filaments is regulated by neurabin II. 54
15632197 2005
44
Genetic malformations of the cerebral cortex and epilepsy. 61
15816977 2005
45
Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes. 54
15607950 2005
46
Neocortical neuronal arrangement in LIS1 and DCX lissencephaly may be different. 61
15057976 2004
47
Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons. 54
14741102 2004
48
The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes. 54
14631200 2003
49
Epilepsy and malformations of the cerebral cortex. 61
14617417 2003
50
Catalytic and regulatory domains of doublecortin kinase-1. 54
12590608 2003

Variations for Lissencephaly, X-Linked, 1

ClinVar genetic disease variations for Lissencephaly, X-Linked, 1:

6 (show all 18) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PAFAH1B1 NM_000430.4(PAFAH1B1):c.505T>C (p.Ser169Pro)SNV Pathogenic 8076 rs121434484 17:2573562-2573562 17:2670268-2670268
2 PAFAH1B1 NM_000430.4(PAFAH1B1):c.722G>C (p.Arg241Pro)SNV Pathogenic 8080 rs121434488 17:2577404-2577404 17:2674110-2674110
3 PAFAH1B1 NM_000430.4(PAFAH1B1):c.22C>T (p.Arg8Ter)SNV Pathogenic 8081 rs121434489 17:2541604-2541604 17:2638310-2638310
4 DCX NM_178152.3(DCX):c.184G>A (p.Asp62Asn)SNV Pathogenic 11597 rs104894779 X:110653443-110653443 X:111410215-111410215
5 DCX NM_178152.3(DCX):c.574C>T (p.Arg192Trp)SNV Pathogenic 11598 rs104894780 X:110644349-110644349 X:111401121-111401121
6 DCX NM_178152.3(DCX):c.373T>C (p.Tyr125His)SNV Pathogenic 11599 rs104894781 X:110644550-110644550 X:111401322-111401322
7 DCX NM_178152.3(DCX):c.176G>T (p.Arg59Leu)SNV Pathogenic 11601 rs122457137 X:110653451-110653451 X:111410223-111410223
8 DCX NM_178152.3(DCX):c.608C>G (p.Thr203Arg)SNV Pathogenic 11602 rs104894782 X:110644315-110644315 X:111401087-111401087
9 DCX NM_178152.3(DCX):c.139A>C (p.Ser47Arg)SNV Pathogenic 11603 rs104894783 X:110653488-110653488 X:111410260-111410260
10 DCX NM_178152.3(DCX):c.587G>A (p.Arg196His)SNV Pathogenic 11609 rs56030372 X:110644336-110644336 X:111401108-111401108
11 DCX NM_178152.3(DCX):c.211G>T (p.Ala71Ser)SNV Pathogenic 11610 rs104894786 X:110653416-110653416 X:111410188-111410188
12 DCX NM_178152.3(DCX):c.682_683CT[1] (p.Tyr229fs)short repeat Pathogenic 434900 rs1556401744 X:110644238-110644239 X:111401010-111401011
13 DCX NM_178152.3(DCX):c.544G>T (p.Val182Phe)SNV Pathogenic 434901 rs1556401951 X:110644379-110644379 X:111401151-111401151
14 DCX NM_178152.3(DCX):c.226C>G (p.Arg76Gly)SNV Pathogenic 619981 rs587783534 X:110653401-110653401 X:111410173-111410173
15 DCX NM_178152.3(DCX):c.809-1G>ASNV Pathogenic/Likely pathogenic 158508 rs587783589 X:110574270-110574270 X:111331042-111331042
16 DCX NM_178152.3(DCX):c.190T>A (p.Tyr64Asn)SNV Likely pathogenic 438585 rs1556405129 X:110653437-110653437 X:111410209-111410209
17 DCX NM_178152.3(DCX):c.-22-364C>TSNV Likely pathogenic 495232 rs761786389 X:110654012-110654012 X:111410784-111410784
18 DCX NM_178152.3(DCX):c.557G>A (p.Arg186His)SNV Conflicting interpretations of pathogenicity 158477 rs587783563 X:110644366-110644366 X:111401138-111401138

UniProtKB/Swiss-Prot genetic disease variations for Lissencephaly, X-Linked, 1:

73 (show all 42)
# Symbol AA change Variation ID SNP ID
1 DCX p.Leu43Ser VAR_007819 rs587783521
2 DCX p.Ser47Arg VAR_007820 rs104894783
3 DCX p.Arg59Leu VAR_007821 rs122457137
4 DCX p.Arg59His VAR_007822 rs122457137
5 DCX p.Asp62Asn VAR_007823 rs104894779
6 DCX p.Arg78Leu VAR_007824 rs104894784
7 DCX p.Asp86His VAR_007825
8 DCX p.Gly100Ala VAR_007826
9 DCX p.Arg102Ser VAR_007827
10 DCX p.Tyr125His VAR_007828 rs104894781
11 DCX p.Tyr125Asp VAR_007829
12 DCX p.Arg178Leu VAR_007830 rs587783559
13 DCX p.Arg186Cys VAR_007831 rs587783562
14 DCX p.Pro191Arg VAR_007832 rs587783566
15 DCX p.Arg192Trp VAR_007833 rs104894780
16 DCX p.Asn200Lys VAR_007834
17 DCX p.Thr203Arg VAR_007835 rs104894782
18 DCX p.Ile214Thr VAR_007836 rs587783574
19 DCX p.Thr222Ile VAR_007837
20 DCX p.Gly223Glu VAR_007838
21 DCX p.Val236Ile VAR_007839 rs132415905
22 DCX p.Ile250Asn VAR_007840
23 DCX p.Ile250Thr VAR_007841
24 DCX p.Gly253Asp VAR_007842
25 DCX p.Arg89Gly VAR_010536 rs104894785
26 DCX p.Thr42Ile VAR_026022
27 DCX p.Lys50Asn VAR_026023 rs587783523
28 DCX p.Asn60Asp VAR_026024
29 DCX p.Gly67Glu VAR_026025
30 DCX p.Ala71Ser VAR_026026 rs104894786
31 DCX p.Leu97Arg VAR_026027 rs587783537
32 DCX p.Ile104Thr VAR_026028
33 DCX p.Arg178Cys VAR_026029 rs587783558
34 DCX p.Pro191Leu VAR_026030
35 DCX p.Arg196His VAR_026031 rs56030372
36 DCX p.Asn200Ile VAR_026033
37 DCX p.Thr203Ala VAR_026034 rs587783570
38 DCX p.Gly223Val VAR_026035
39 DCX p.Phe243Leu VAR_026036
40 DCX p.Ala251Ser VAR_026037 rs587783585
41 DCX p.Ala251Val VAR_026038
42 DCX p.Asp262Gly VAR_077482 rs398124557

Copy number variations for Lissencephaly, X-Linked, 1 from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 257508 X 103600000 116800000 Copy number DCX X-linked lissencephaly
2 261298 X 17100000 19200000 Copy number ARX X-linked lissencephaly
3 261366 X 18331857 18460326 Deletion CDKL5 X-linked lissencephaly
4 261706 X 24900000 37500000 Copy number ARX X-linked lissencephaly
5 266516 X 98200000 110500000 Copy number DCX X-linked lissencephaly

Expression for Lissencephaly, X-Linked, 1

Search GEO for disease gene expression data for Lissencephaly, X-Linked, 1.

Pathways for Lissencephaly, X-Linked, 1

Pathways related to Lissencephaly, X-Linked, 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.44 PAFAH1B1 DCX
2 10.11 PAFAH1B1 DCX

GO Terms for Lissencephaly, X-Linked, 1

Cellular components related to Lissencephaly, X-Linked, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule associated complex GO:0005875 8.62 PAFAH1B1 DCX

Biological processes related to Lissencephaly, X-Linked, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.54 PAFAH1B1 DCX ARX
2 cell differentiation GO:0030154 9.5 PAFAH1B1 DCX ARX
3 brain development GO:0007420 9.4 PAFAH1B1 DCX
4 nervous system development GO:0007399 9.33 PAFAH1B1 DCX ARX
5 hippocampus development GO:0021766 9.26 PAFAH1B1 DCX
6 layer formation in cerebral cortex GO:0021819 8.96 PAFAH1B1 DCX
7 neuron migration GO:0001764 8.8 PAFAH1B1 DCX ARX

Molecular functions related to Lissencephaly, X-Linked, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule binding GO:0008017 8.62 PAFAH1B1 DCX

Sources for Lissencephaly, X-Linked, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
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
71 UMLS
72 UMLS via Orphanet
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