MCID: LSS005
MIFTS: 43

Lissencephaly 1

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Fetal diseases, Cardiovascular diseases, Skin diseases, Muscle diseases

Aliases & Classifications for Lissencephaly 1

MalaCards integrated aliases for Lissencephaly 1:

Name: Lissencephaly 1 57 53 75 29 13 6
Lis1 57 53 25 75
Ils 57 53 25
Lissencephaly Sequence, Isolated 57 55
Subcortical Laminar Heterotopia 57 75
Subcortical Band Heterotopia 75 73
Classical Lissencephaly 25 73
Lissencephaly, Classic 57 25
Classic Lissencephaly 53 75
Double Cortex 75 73
Lissencephaly Sequence, Isolated; Ils 57
Lissencephaly Due to Lis1 Mutation 59
Lissencephaly Sequence Isolated 53
Isolated Lissencephaly Sequence 25
Pafah1b1-Related Lissencephaly 59
Lissencephaly Syndrome Type 1 76
Lissencephaly Classic 53
Lissencephaly, Type 1 40
Lissencephaly Type 1 25
Type 1 Lissencephaly 25
Type I Lissencephaly 73
Lissencephaly-1 75
Sclh 75
Sbh 75

Characteristics:

OMIM:

57
Miscellaneous:
variable severity
all reported cases have resulted from de novo mutations

Inheritance:
isolated cases


HPO:

32
lissencephaly 1:
Onset and clinical course variable expressivity
Inheritance sporadic


Classifications:



Summaries for Lissencephaly 1

OMIM : 57 Lissencephaly (LIS), literally meaning smooth brain, is characterized by smooth or nearly smooth cerebral surface and a paucity of gyral and sulcal development, encompassing a spectrum of brain surface malformations ranging from complete agyria to subcortical band heterotopia (SBH). Classic lissencephaly is associated with an abnormally thick cortex, reduced or abnormal lamination, and diffuse neuronal heterotopia. SBH consists of circumferential bands of heterotopic neurons located just beneath the cortex and separated from it by a thin band of white matter. SBH represents the less severe end of the lissencephaly spectrum of malformations (Pilz et al., 1999, summary by Kato and Dobyns, 2003). Agyria, i.e., brain without convolutions or gyri, was considered a rare malformation until recent progress in neuroradiology (Bordarier et al., 1986). With this technical advantage, a number of lissencephaly syndromes have been distinguished. Classic lissencephaly (formerly type I) is a brain malformation caused by abnormal neuronal migration at 9 to 13 weeks' gestation, resulting in a spectrum of agyria, mixed agyria/pachygyria, and pachygyria. It is characterized by an abnormally thick and poorly organized cortex with 4 primitive layers, diffuse neuronal heterotopia, enlarged and dysmorphic ventricles, and often hypoplasia of the corpus callosum. (Lo Nigro et al., 1997). Kato and Dobyns (2003) presented a classification system for neuronal migration disorders based on brain imaging findings and molecular analysis. The authors also reviewed the contributions and interactions of the 5 genes then known to cause human lissencephaly: LIS1 or PAFAH1B1, 14-3-3-epsilon (YWHAE), DCX, RELN, and ARX. (607432)

MalaCards based summary : Lissencephaly 1, also known as lis1, is related to lissencephaly, x-linked, 1 and band heterotopia. An important gene associated with Lissencephaly 1 is PAFAH1B1 (Platelet Activating Factor Acetylhydrolase 1b Regulatory Subunit 1), and among its related pathways/superpathways are Neuroscience and Cytoskeletal Signaling. Affiliated tissues include brain, cortex and liver, and related phenotypes are intellectual disability and seizures

UniProtKB/Swiss-Prot : 75 Lissencephaly 1: A classical lissencephaly. It is characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six- layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. Associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum. Subcortical band heterotopia: SBH 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.

Genetics Home Reference : 25 Isolated lissencephaly sequence (ILS) is a condition that affects brain development before birth. Normally, the cells that make up the exterior of the brain (cerebral cortex) are well-organized, multi-layered, and arranged into many folds and grooves (gyri). In people with ILS, the cells of the cerebral cortex are disorganized, and the brain surface is abnormally smooth with an absence (agyria) or reduction (pachygyria) of folds and grooves. In most cases, these abnormalities impair brain growth, causing the brain to be smaller than normal (microcephaly). This underdevelopment of the brain causes severe intellectual disability, delayed development, and recurrent seizures (epilepsy) in individuals with ILS.

Wikipedia : 76 Lissencephaly is a set of rare brain disorders where the whole or parts of the surface of the brain... more...

Related Diseases for Lissencephaly 1

Graphical network of the top 20 diseases related to Lissencephaly 1:



Diseases related to Lissencephaly 1

Symptoms & Phenotypes for Lissencephaly 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
cerebellar hypoplasia
pachygyria
enlarged ventricles
mental retardation
seizures, refractory
more
Head And Neck Head:
microcephaly, postnatal

Neurologic Behavioral Psychiatric Manifestations:
autistic features


Clinical features from OMIM:

607432

Human phenotypes related to Lissencephaly 1:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 seizures 32 HP:0001250
3 global developmental delay 32 HP:0001263
4 spastic tetraparesis 32 HP:0001285
5 pachygyria 32 HP:0001302
6 cerebellar hypoplasia 32 HP:0001321
7 ventriculomegaly 32 HP:0002119
8 heterotopia 32 HP:0002282
9 hypoplasia of the brainstem 32 HP:0002365
10 abnormality of the cerebral white matter 32 HP:0002500
11 postnatal microcephaly 32 HP:0005484
12 muscular hypotonia of the trunk 32 HP:0008936

MGI Mouse Phenotypes related to Lissencephaly 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.1 BICD1 DCX DISC1 FEZ1 PAFAH1B1 RELN

Drugs & Therapeutics for Lissencephaly 1

Search Clinical Trials , NIH Clinical Center for Lissencephaly 1

Genetic Tests for Lissencephaly 1

Genetic tests related to Lissencephaly 1:

# Genetic test Affiliating Genes
1 Lissencephaly 1 29 PAFAH1B1

Anatomical Context for Lissencephaly 1

MalaCards organs/tissues related to Lissencephaly 1:

41
Brain, Cortex, Liver

Publications for Lissencephaly 1

Articles related to Lissencephaly 1:

# Title Authors Year
1
Hepatic loss of <i>Lissencephaly 1</i> (<i>Lis1</i>) induces fatty liver and accelerates liver tumorigenesis in mice. ( 29475944 )
2018
2
Lissencephaly 1 linking to multiple diseases: mental retardation, neurodegeneration, schizophrenia, male sterility, and more. ( 17028375 )
2006
3
LIS2, gene and pseudogene, homologous to LIS1 (lissencephaly 1), located on the short and long arms of chromosome 2. ( 8586424 )
1995

Variations for Lissencephaly 1

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

75
# Symbol AA change Variation ID SNP ID
1 PAFAH1B1 p.His149Arg VAR_007724 rs121434482
2 PAFAH1B1 p.Ser169Pro VAR_010203 rs121434484
3 PAFAH1B1 p.Phe31Ser VAR_015398 rs121434486
4 PAFAH1B1 p.Gly162Ser VAR_015399 rs121434487
5 PAFAH1B1 p.Asp317His VAR_015400 rs121434485
6 PAFAH1B1 p.Arg241Pro VAR_037300 rs121434488
7 PAFAH1B1 p.His277Pro VAR_037301 rs121434490

ClinVar genetic disease variations for Lissencephaly 1:

6
(show top 50) (show all 209)
# Gene Variation Type Significance SNP ID Assembly Location
1 PAFAH1B1 NM_000430.3(PAFAH1B1): c.446A> G (p.His149Arg) single nucleotide variant Pathogenic rs121434482 GRCh37 Chromosome 17, 2573503: 2573503
2 PAFAH1B1 NM_000430.3(PAFAH1B1): c.446A> G (p.His149Arg) single nucleotide variant Pathogenic rs121434482 GRCh38 Chromosome 17, 2670209: 2670209
3 PAFAH1B1 NM_000430.3(PAFAH1B1): c.817C> T (p.Arg273Ter) single nucleotide variant Pathogenic rs121434483 GRCh37 Chromosome 17, 2577499: 2577499
4 PAFAH1B1 NM_000430.3(PAFAH1B1): c.817C> T (p.Arg273Ter) single nucleotide variant Pathogenic rs121434483 GRCh38 Chromosome 17, 2674205: 2674205
5 PAFAH1B1 PAFAH1B1, 22-BP DEL deletion Pathogenic
6 PAFAH1B1 NM_000430.3(PAFAH1B1): c.949G> C (p.Asp317His) single nucleotide variant Pathogenic rs121434485 GRCh37 Chromosome 17, 2579847: 2579847
7 PAFAH1B1 NM_000430.3(PAFAH1B1): c.949G> C (p.Asp317His) single nucleotide variant Pathogenic rs121434485 GRCh38 Chromosome 17, 2676553: 2676553
8 PAFAH1B1 NM_000430.3(PAFAH1B1): c.92T> C (p.Phe31Ser) single nucleotide variant Pathogenic rs121434486 GRCh37 Chromosome 17, 2568725: 2568725
9 PAFAH1B1 NM_000430.3(PAFAH1B1): c.92T> C (p.Phe31Ser) single nucleotide variant Pathogenic rs121434486 GRCh38 Chromosome 17, 2665431: 2665431
10 PAFAH1B1 NM_000430.3(PAFAH1B1): c.484G> A (p.Gly162Ser) single nucleotide variant Pathogenic rs121434487 GRCh37 Chromosome 17, 2573541: 2573541
11 PAFAH1B1 NM_000430.3(PAFAH1B1): c.484G> A (p.Gly162Ser) single nucleotide variant Pathogenic rs121434487 GRCh38 Chromosome 17, 2670247: 2670247
12 PAFAH1B1 NM_000430.3(PAFAH1B1): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs121434489 GRCh37 Chromosome 17, 2541604: 2541604
13 PAFAH1B1 NM_000430.3(PAFAH1B1): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs121434489 GRCh38 Chromosome 17, 2638310: 2638310
14 PAFAH1B1 NM_000430.3(PAFAH1B1): c.830A> C (p.His277Pro) single nucleotide variant Pathogenic rs121434490 GRCh37 Chromosome 17, 2577512: 2577512
15 PAFAH1B1 NM_000430.3(PAFAH1B1): c.830A> C (p.His277Pro) single nucleotide variant Pathogenic rs121434490 GRCh38 Chromosome 17, 2674218: 2674218
16 PAFAH1B1 NM_000430.3(PAFAH1B1): c.1002+1G> A single nucleotide variant Pathogenic rs113994203 GRCh37 Chromosome 17, 2579901: 2579901
17 PAFAH1B1 NM_000430.3(PAFAH1B1): c.1002+1G> A single nucleotide variant Pathogenic rs113994203 GRCh38 Chromosome 17, 2676607: 2676607
18 PAFAH1B1 NM_000430.3(PAFAH1B1): c.1050delG (p.Lys351Serfs) deletion Pathogenic rs113994200 GRCh37 Chromosome 17, 2583505: 2583505
19 PAFAH1B1 NM_000430.3(PAFAH1B1): c.1050delG (p.Lys351Serfs) deletion Pathogenic rs113994200 GRCh38 Chromosome 17, 2680211: 2680211
20 PAFAH1B1 NM_000430.3(PAFAH1B1): c.1050dupG (p.Lys351Glufs) duplication Pathogenic rs113994201 GRCh37 Chromosome 17, 2583505: 2583505
21 PAFAH1B1 NM_000430.3(PAFAH1B1): c.1050dupG (p.Lys351Glufs) duplication Pathogenic rs113994201 GRCh38 Chromosome 17, 2680211: 2680211
22 PAFAH1B1 NM_000430.3(PAFAH1B1): c.162delA (p.Lys54Asnfs) deletion Pathogenic rs113994198 GRCh37 Chromosome 17, 2569354: 2569354
23 PAFAH1B1 NM_000430.3(PAFAH1B1): c.162delA (p.Lys54Asnfs) deletion Pathogenic rs113994198 GRCh38 Chromosome 17, 2666060: 2666060
24 PAFAH1B1 NM_000430.3(PAFAH1B1): c.162dupA (p.Trp55Metfs) duplication Pathogenic rs113994199 GRCh37 Chromosome 17, 2569354: 2569354
25 PAFAH1B1 NM_000430.3(PAFAH1B1): c.162dupA (p.Trp55Metfs) duplication Pathogenic rs113994199 GRCh38 Chromosome 17, 2666060: 2666060
26 PAFAH1B1 NM_000430.3(PAFAH1B1): c.569-10T> C single nucleotide variant Pathogenic/Likely pathogenic rs113994202 GRCh37 Chromosome 17, 2575939: 2575939
27 PAFAH1B1 NM_000430.3(PAFAH1B1): c.569-10T> C single nucleotide variant Pathogenic/Likely pathogenic rs113994202 GRCh38 Chromosome 17, 2672645: 2672645
28 PAFAH1B1 NM_000430.3(PAFAH1B1): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs587784265 GRCh37 Chromosome 17, 2541585: 2541585
29 PAFAH1B1 NM_000430.3(PAFAH1B1): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs587784265 GRCh38 Chromosome 17, 2638291: 2638291
30 PAFAH1B1 NM_000430.3(PAFAH1B1): c.33-3C> T single nucleotide variant Pathogenic rs587784260 GRCh37 Chromosome 17, 2568663: 2568663
31 PAFAH1B1 NM_000430.3(PAFAH1B1): c.33-3C> T single nucleotide variant Pathogenic rs587784260 GRCh38 Chromosome 17, 2665369: 2665369
32 PAFAH1B1 NM_000430.3(PAFAH1B1): c.37C> T (p.Arg13Ter) single nucleotide variant Pathogenic rs587784262 GRCh37 Chromosome 17, 2568670: 2568670
33 PAFAH1B1 NM_000430.3(PAFAH1B1): c.37C> T (p.Arg13Ter) single nucleotide variant Pathogenic rs587784262 GRCh38 Chromosome 17, 2665376: 2665376
34 PAFAH1B1 NM_000430.3(PAFAH1B1): c.56T> G (p.Leu19Arg) single nucleotide variant Pathogenic rs587784272 GRCh37 Chromosome 17, 2568689: 2568689
35 PAFAH1B1 NM_000430.3(PAFAH1B1): c.56T> G (p.Leu19Arg) single nucleotide variant Pathogenic rs587784272 GRCh38 Chromosome 17, 2665395: 2665395
36 PAFAH1B1 NM_000430.3(PAFAH1B1): c.72T> G (p.Tyr24Ter) single nucleotide variant Pathogenic rs587784285 GRCh37 Chromosome 17, 2568705: 2568705
37 PAFAH1B1 NM_000430.3(PAFAH1B1): c.72T> G (p.Tyr24Ter) single nucleotide variant Pathogenic rs587784285 GRCh38 Chromosome 17, 2665411: 2665411
38 PAFAH1B1 NM_000430.3(PAFAH1B1): c.84T> G (p.Tyr28Ter) single nucleotide variant Pathogenic rs369259961 GRCh37 Chromosome 17, 2568717: 2568717
39 PAFAH1B1 NM_000430.3(PAFAH1B1): c.84T> G (p.Tyr28Ter) single nucleotide variant Pathogenic rs369259961 GRCh38 Chromosome 17, 2665423: 2665423
40 PAFAH1B1 NM_000430.3(PAFAH1B1): c.121G> A (p.Glu41Lys) single nucleotide variant Likely pathogenic rs587784250 GRCh37 Chromosome 17, 2569313: 2569313
41 PAFAH1B1 NM_000430.3(PAFAH1B1): c.121G> A (p.Glu41Lys) single nucleotide variant Likely pathogenic rs587784250 GRCh38 Chromosome 17, 2666019: 2666019
42 PAFAH1B1 NM_000430.3(PAFAH1B1): c.136_137delAA (p.Lys46Valfs) deletion Pathogenic rs587784252 GRCh37 Chromosome 17, 2569328: 2569329
43 PAFAH1B1 NM_000430.3(PAFAH1B1): c.136_137delAA (p.Lys46Valfs) deletion Pathogenic rs587784252 GRCh38 Chromosome 17, 2666034: 2666035
44 PAFAH1B1 NM_000430.3(PAFAH1B1): c.152delT (p.Leu51Trpfs) deletion Pathogenic rs587784253 GRCh37 Chromosome 17, 2569344: 2569344
45 PAFAH1B1 NM_000430.3(PAFAH1B1): c.152delT (p.Leu51Trpfs) deletion Pathogenic rs587784253 GRCh38 Chromosome 17, 2666050: 2666050
46 PAFAH1B1 NM_000430.3(PAFAH1B1): c.163T> A (p.Trp55Arg) single nucleotide variant Pathogenic rs587784254 GRCh37 Chromosome 17, 2569355: 2569355
47 PAFAH1B1 NM_000430.3(PAFAH1B1): c.163T> A (p.Trp55Arg) single nucleotide variant Pathogenic rs587784254 GRCh38 Chromosome 17, 2666061: 2666061
48 PAFAH1B1 NM_000430.3(PAFAH1B1): c.192G> C (p.Lys64Asn) single nucleotide variant Pathogenic rs587784257 GRCh37 Chromosome 17, 2569384: 2569384
49 PAFAH1B1 NM_000430.3(PAFAH1B1): c.192G> C (p.Lys64Asn) single nucleotide variant Pathogenic rs587784257 GRCh38 Chromosome 17, 2666090: 2666090
50 PAFAH1B1 NM_000430.3(PAFAH1B1): c.192+1G> A single nucleotide variant Pathogenic rs587784256 GRCh37 Chromosome 17, 2569385: 2569385

Expression for Lissencephaly 1

Search GEO for disease gene expression data for Lissencephaly 1.

Pathways for Lissencephaly 1

Pathways related to Lissencephaly 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 12.03 DCX FEZ1 PAFAH1B1
2 11.92 DCX FEZ1 PAFAH1B1
3 10.62 PAFAH1B1 RELN
4 10.42 DCX PAFAH1B1 PLA2G7 RELN
5 10.4 BICD1 PAFAH1B1

GO Terms for Lissencephaly 1

Cellular components related to Lissencephaly 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.55 BICD1 DCX DISC1 FEZ1 PAFAH1B1
2 microtubule organizing center GO:0005815 9.5 DISC1 FEZ1 PAFAH1B1
3 microtubule associated complex GO:0005875 9.26 DCX PAFAH1B1
4 centrosome GO:0005813 9.26 BICD1 DISC1 FEZ1 PAFAH1B1
5 microtubule GO:0005874 8.92 DCX DISC1 FEZ1 PAFAH1B1

Biological processes related to Lissencephaly 1 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.78 DCX DISC1 PAFAH1B1 RELN
2 nervous system development GO:0007399 9.67 DCX DISC1 FEZ1 PAFAH1B1
3 brain development GO:0007420 9.61 DCX PAFAH1B1 RELN
4 positive regulation of neuron projection development GO:0010976 9.51 FEZ1 RELN
5 microtubule cytoskeleton organization GO:0000226 9.49 DISC1 PAFAH1B1
6 cerebral cortex development GO:0021987 9.46 PAFAH1B1 RELN
7 neuron migration GO:0001764 9.46 DCX DISC1 PAFAH1B1 RELN
8 regulation of microtubule cytoskeleton organization GO:0070507 9.4 BICD1 PAFAH1B1
9 positive regulation of dendritic spine morphogenesis GO:0061003 9.32 PAFAH1B1 RELN
10 platelet activating factor metabolic process GO:0046469 9.26 PAFAH1B1 PLA2G7
11 layer formation in cerebral cortex GO:0021819 9.13 DCX PAFAH1B1 RELN
12 hippocampus development GO:0021766 8.92 DCX FEZ1 PAFAH1B1 RELN

Molecular functions related to Lissencephaly 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 dynein intermediate chain binding GO:0045505 9.16 BICD1 PAFAH1B1
2 dynein complex binding GO:0070840 8.96 BICD1 PAFAH1B1
3 dynactin binding GO:0034452 8.62 BICD1 PAFAH1B1

Sources for Lissencephaly 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
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....