LISX1
MCID: LSS036
MIFTS: 47

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 57
Lissencephaly, X-Linked 57 29 13 55 6
Xlis 57 53 75
Lissencephaly and Agenesis of Corpus Callosum 57 53
Subcortical Laminar Heterotopia, X-Linked 29 6
X-Linked Lissencephaly 53 73
Double Cortex 75 73
Lisx1 57 75
Lissencephaly Type 1 Due to Doublecortin Gene Mutation 59
Subcortical Laminar Heterotopia, X-Linked, 53
Subcortical Laminal Heterotopia, X-Linked 57
Subcortical Band Heterotopia X-Linked 75
Lissencephaly, X-Linked, Type 1 ) 40
Subcortical Laminar Heterotopia 75
X-Linked Lissencephaly Type 1 59
Subcortical Band Heterotopia 73
Lissencephaly, X-Linked 1 75
Lissencephaly X-Linked 53
Lisx 53
Sclh 75
Sbhx 75

Characteristics:

Orphanet epidemiological data:

59
lissencephaly type 1 due to doublecortin gene mutation
Inheritance: X-linked recessive; Age of onset: Adolescent,Childhood,Infancy,Neonatal;

OMIM:

57
Miscellaneous:
onset in infancy
incomplete penetrance
highly variable phenotype in females
somatic or germline mosaicism may occur

Inheritance:
x-linked


HPO:

32
lissencephaly, x-linked, 1:
Mortality/Aging death in infancy
Onset and clinical course incomplete penetrance infantile onset
Inheritance x-linked inheritance


Classifications:



Summaries for Lissencephaly, X-Linked, 1

Genetics Home Reference : 25 Subcortical band heterotopia is a condition in which nerve cells (neurons) do not move (migrate) to their proper locations in the fetal brain during early development. (Heterotopia means "out of place.") Normally, the neurons that make up the outer surface of the brain (cerebral cortex) are distributed in a well-organized and multi-layered way. In people with subcortical band heterotopia, some neurons that should be part of the cerebral cortex do not reach it. These neurons stop their migration process in areas of the brain where they are not supposed to be and form band-like clusters of tissue. Since these bands are located beneath the cerebral cortex, they are said to be subcortical. In most cases, the bands are symmetric, which means they occur in the same places on the right and left sides of the brain.

MalaCards based summary : Lissencephaly, X-Linked, 1, also known as lissencephaly, x-linked, is related to lissencephaly 1 and band heterotopia, 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 Neuroscience and Cytoskeletal Signaling. Affiliated tissues include cortex, brain and fetal brain, and related phenotypes are seizures and muscular hypotonia

OMIM : 57 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)

UniProtKB/Swiss-Prot : 75 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.

Related Diseases for Lissencephaly, X-Linked, 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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus

Neurologic Central Nervous System:
seizures
ataxia
dysarthria
pachygyria
delayed motor development
more

Clinical features from OMIM:

300067

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

59 32 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
3 hypertonia 59 32 frequent (33%) Frequent (79-30%) HP:0001276
4 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
5 feeding difficulties 59 32 frequent (33%) Frequent (79-30%) HP:0011968
6 agenesis of corpus callosum 32 HP:0001274
7 nystagmus 32 HP:0000639
8 intellectual disability 32 HP:0001249
9 ataxia 32 HP:0001251
10 spasticity 32 HP:0001257
11 dysarthria 32 HP:0001260
12 postnatal growth retardation 32 HP:0008897
13 motor delay 32 HP:0001270
14 pachygyria 32 HP:0001302
15 micropenis 32 HP:0000054
16 heterotopia 32 HP:0002282
17 muscular hypotonia of the trunk 32 HP:0008936
18 agyria 32 HP:0031882

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 DCX
2 Subcortical Laminar Heterotopia, X-Linked 29

Anatomical Context for Lissencephaly, X-Linked, 1

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

41
Cortex, Brain, Fetal Brain, Thyroid, Thalamus, Testes, Hypothalamus

Publications for Lissencephaly, X-Linked, 1

Articles related to Lissencephaly, X-Linked, 1:

(show all 23)
# Title Authors Year
1
A Neonate with X-linked Lissencephaly with Ambiguous Genitalia. ( 28553390 )
2017
2
X-Linked Lissencephaly With Absent Corpus Callosum and Abnormal Genitalia: An Evolving Multisystem Syndrome With Severe Congenital Intestinal Diarrhea Disease. ( 29152528 )
2017
3
A novel DCX missense mutation in a family with X-linked lissencephaly and subcortical band heterotopia syndrome inherited from a low-level somatic mosaic mother: Genetic and functional studies. ( 27292316 )
2016
4
Watery diarrhea-hypopotassemia-acidosis syndrome like diarrhea in a case with X-linked lissencephaly with abnormal genitalia. ( 26129807 )
2015
5
Analysis of the hypothalamus in a case of X-linked lissencephaly with abnormal genitalia (XLAG). ( 18842366 )
2009
6
Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG). ( 18458920 )
2008
7
Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate. ( 18412232 )
2008
8
The location of DCX mutations predicts malformation severity in X-linked lissencephaly. ( 18685874 )
2008
9
Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. ( 17460091 )
2007
10
[X-linked lissencephaly with absent corpus callosum and abnormal genitalia: a report of siblings followed from the prenatal period]. ( 17515135 )
2007
11
Central and gonadal hypogonadism in X-linked lissencephaly. ( 16995578 )
2006
12
X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, "interneuronopathy". ( 15921244 )
2005
13
X-linked lissencephaly with abnormal genitalia associated with renal phosphate wasting. ( 15248105 )
2004
14
ARX mutations in X-linked lissencephaly with abnormal genitalia. ( 12874405 )
2003
15
X-linked lissencephaly in an Indian family. ( 14652450 )
2003
16
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. ( 11891829 )
2002
17
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. ( 12379852 )
2002
18
X-linked lissencephaly with ambiguous genitalia: delineation of further case. ( 10982975 )
2000
19
Differences in the gyral pattern distinguish chromosome 17-linked and X-linked lissencephaly. ( 10430413 )
1999
20
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia. ( 10494089 )
1999
21
A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia. ( 10369164 )
1999
22
Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. ( 9489700 )
1998
23
Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain. ( 9097958 )
1997

Variations for Lissencephaly, X-Linked, 1

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

75 (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

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

6 (show all 48)
# Gene Variation Type Significance SNP ID Assembly Location
1 PAFAH1B1 NM_000430.3(PAFAH1B1): c.505T> C (p.Ser169Pro) single nucleotide variant Pathogenic rs121434484 GRCh37 Chromosome 17, 2573562: 2573562
2 PAFAH1B1 NM_000430.3(PAFAH1B1): c.505T> C (p.Ser169Pro) single nucleotide variant Pathogenic rs121434484 GRCh38 Chromosome 17, 2670268: 2670268
3 PAFAH1B1 NM_000430.3(PAFAH1B1): c.722G> C (p.Arg241Pro) single nucleotide variant Pathogenic rs121434488 GRCh37 Chromosome 17, 2577404: 2577404
4 PAFAH1B1 NM_000430.3(PAFAH1B1): c.722G> C (p.Arg241Pro) single nucleotide variant Pathogenic rs121434488 GRCh38 Chromosome 17, 2674110: 2674110
5 PAFAH1B1 NM_000430.3(PAFAH1B1): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs121434489 GRCh37 Chromosome 17, 2541604: 2541604
6 PAFAH1B1 NM_000430.3(PAFAH1B1): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs121434489 GRCh38 Chromosome 17, 2638310: 2638310
7 DCX NM_178152.2(DCX): c.184G> A (p.Asp62Asn) single nucleotide variant Pathogenic rs104894779 GRCh37 Chromosome X, 110653443: 110653443
8 DCX NM_178152.2(DCX): c.184G> A (p.Asp62Asn) single nucleotide variant Pathogenic rs104894779 GRCh38 Chromosome X, 111410215: 111410215
9 DCX NM_178151.2(DCX): c.574C> T (p.Arg192Trp) single nucleotide variant Pathogenic rs104894780 GRCh37 Chromosome X, 110644349: 110644349
10 DCX NM_178151.2(DCX): c.574C> T (p.Arg192Trp) single nucleotide variant Pathogenic rs104894780 GRCh38 Chromosome X, 111401121: 111401121
11 DCX NM_178152.2(DCX): c.373T> C (p.Tyr125His) single nucleotide variant Pathogenic rs104894781 GRCh37 Chromosome X, 110644550: 110644550
12 DCX NM_178152.2(DCX): c.373T> C (p.Tyr125His) single nucleotide variant Pathogenic rs104894781 GRCh38 Chromosome X, 111401322: 111401322
13 DCX DCX, IVS4, G-A, +1 single nucleotide variant Pathogenic
14 DCX NM_178152.2(DCX): c.176G> T (p.Arg59Leu) single nucleotide variant Pathogenic rs122457137 GRCh37 Chromosome X, 110653451: 110653451
15 DCX NM_178152.2(DCX): c.176G> T (p.Arg59Leu) single nucleotide variant Pathogenic rs122457137 GRCh38 Chromosome X, 111410223: 111410223
16 DCX NM_178152.2(DCX): c.608C> G (p.Thr203Arg) single nucleotide variant Pathogenic rs104894782 GRCh37 Chromosome X, 110644315: 110644315
17 DCX NM_178152.2(DCX): c.608C> G (p.Thr203Arg) single nucleotide variant Pathogenic rs104894782 GRCh38 Chromosome X, 111401087: 111401087
18 DCX NM_178152.2(DCX): c.139A> C (p.Ser47Arg) single nucleotide variant Pathogenic rs104894783 GRCh37 Chromosome X, 110653488: 110653488
19 DCX NM_178152.2(DCX): c.139A> C (p.Ser47Arg) single nucleotide variant Pathogenic rs104894783 GRCh38 Chromosome X, 111410260: 111410260
20 DCX DCX, 2-BP INS, 36AG insertion Pathogenic
21 DCX DCX, 2-BP DEL, 684CT deletion Pathogenic
22 DCX DCX, 2-BP DEL, 691CT deletion Pathogenic
23 DCX NM_178152.2(DCX): c.233G> A (p.Arg78His) single nucleotide variant Pathogenic rs104894784 GRCh37 Chromosome X, 110653394: 110653394
24 DCX NM_178152.2(DCX): c.233G> A (p.Arg78His) single nucleotide variant Pathogenic rs104894784 GRCh38 Chromosome X, 111410166: 111410166
25 DCX NM_178152.2(DCX): c.265C> G (p.Arg89Gly) single nucleotide variant Pathogenic rs104894785 GRCh37 Chromosome X, 110653362: 110653362
26 DCX NM_178152.2(DCX): c.265C> G (p.Arg89Gly) single nucleotide variant Pathogenic rs104894785 GRCh38 Chromosome X, 111410134: 111410134
27 DCX NM_178151.2(DCX): c.587G> A (p.Arg196His) single nucleotide variant Pathogenic rs56030372 GRCh37 Chromosome X, 110644336: 110644336
28 DCX NM_178151.2(DCX): c.587G> A (p.Arg196His) single nucleotide variant Pathogenic rs56030372 GRCh38 Chromosome X, 111401108: 111401108
29 DCX NM_178152.2(DCX): c.211G> T (p.Ala71Ser) single nucleotide variant Pathogenic rs104894786 GRCh37 Chromosome X, 110653416: 110653416
30 DCX NM_178152.2(DCX): c.211G> T (p.Ala71Ser) single nucleotide variant Pathogenic rs104894786 GRCh38 Chromosome X, 111410188: 111410188
31 DCX NM_178151.2(DCX): c.809-1G> A single nucleotide variant Pathogenic/Likely pathogenic rs587783589 GRCh37 Chromosome X, 110574270: 110574270
32 DCX NM_178151.2(DCX): c.809-1G> A single nucleotide variant Pathogenic/Likely pathogenic rs587783589 GRCh38 Chromosome X, 111331042: 111331042
33 DCX NM_178151.2(DCX): c.781C> T (p.Gln261Ter) single nucleotide variant Pathogenic rs587783588 GRCh37 Chromosome X, 110576306: 110576306
34 DCX NM_178151.2(DCX): c.781C> T (p.Gln261Ter) single nucleotide variant Pathogenic rs587783588 GRCh38 Chromosome X, 111333078: 111333078
35 DCX NM_178151.2(DCX): c.557G> A (p.Arg186His) single nucleotide variant Conflicting interpretations of pathogenicity rs587783563 GRCh37 Chromosome X, 110644366: 110644366
36 DCX NM_178151.2(DCX): c.557G> A (p.Arg186His) single nucleotide variant Conflicting interpretations of pathogenicity rs587783563 GRCh38 Chromosome X, 111401138: 111401138
37 DCX NM_178151.2(DCX): c.705+1del deletion Pathogenic GRCh37 Chromosome X, 110644217: 110644217
38 DCX NM_178151.2(DCX): c.705+1del deletion Pathogenic GRCh38 Chromosome X, 111400989: 111400989
39 DCX NM_178152.2(DCX): c.684_685delCT (p.Tyr229Hisfs) deletion Pathogenic GRCh37 Chromosome X, 110644238: 110644239
40 DCX NM_178152.2(DCX): c.684_685delCT (p.Tyr229Hisfs) deletion Pathogenic GRCh38 Chromosome X, 111401010: 111401011
41 DCX NM_178151.2(DCX): c.544G> T (p.Val182Phe) single nucleotide variant Pathogenic GRCh37 Chromosome X, 110644379: 110644379
42 DCX NM_178151.2(DCX): c.544G> T (p.Val182Phe) single nucleotide variant Pathogenic GRCh38 Chromosome X, 111401151: 111401151
43 DCX NM_178152.2(DCX): c.355_356delCT (p.Leu119Glyfs) deletion Pathogenic GRCh37 Chromosome X, 110653271: 110653272
44 DCX NM_178152.2(DCX): c.355_356delCT (p.Leu119Glyfs) deletion Pathogenic GRCh38 Chromosome X, 111410043: 111410044
45 DCX NM_000555.3(DCX): c.433T> A (p.Tyr145Asn) single nucleotide variant Likely pathogenic GRCh37 Chromosome X, 110653437: 110653437
46 DCX NM_000555.3(DCX): c.433T> A (p.Tyr145Asn) single nucleotide variant Likely pathogenic GRCh38 Chromosome X, 111410209: 111410209
47 DCX NM_000555.3(DCX): c.191C> T (p.Pro64Leu) single nucleotide variant Likely pathogenic rs761786389 GRCh38 Chromosome X, 111410784: 111410784
48 DCX NM_000555.3(DCX): c.191C> T (p.Pro64Leu) single nucleotide variant Likely pathogenic rs761786389 GRCh37 Chromosome X, 110654012: 110654012

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

7
# CNVD ID Chromosom 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 11.69 DCX PAFAH1B1
2 11.44 DCX PAFAH1B1
3 10.11 DCX PAFAH1B1

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 DCX PAFAH1B1

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 ARX DCX PAFAH1B1
2 cell differentiation GO:0030154 9.5 ARX DCX PAFAH1B1
3 brain development GO:0007420 9.4 DCX PAFAH1B1
4 nervous system development GO:0007399 9.33 ARX DCX PAFAH1B1
5 hippocampus development GO:0021766 9.26 DCX PAFAH1B1
6 layer formation in cerebral cortex GO:0021819 8.96 DCX PAFAH1B1
7 neuron migration GO:0001764 8.8 ARX DCX PAFAH1B1

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 DCX PAFAH1B1

Sources for Lissencephaly, X-Linked, 1

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
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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
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