LIS3
MCID: LSS009
MIFTS: 43

Lissencephaly 3 (LIS3)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Lissencephaly 3

MalaCards integrated aliases for Lissencephaly 3:

Name: Lissencephaly 3 57 11 73 12 43 14 71
Lissencephaly Due to Tuba1a Mutation 58 28 5
Lissencephaly Type 3 58 28 5
Lis3 57 11 73
Lissencephaly, Type 3 38

Characteristics:


Inheritance:

Lissencephaly 3: Autosomal dominant 57
Lissencephaly Due to Tuba1a Mutation: Autosomal dominant 58

Prevelance:

Lissencephaly Due to Tuba1a Mutation: <1/1000000 (Worldwide) 58

Age Of Onset:

Lissencephaly Due to Tuba1a Mutation: Antenatal,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
de novo mutation (in most patients)


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 11 DOID:0112232
OMIM® 57 611603
OMIM Phenotypic Series 57 PS607432
ICD10 via Orphanet 32 Q04.3
UMLS via Orphanet 72 C1969029
MedGen 40 C1969029
UMLS 71 C1969029

Summaries for Lissencephaly 3

Orphanet: 58 Lissencephaly (LIS) due to TUBA1A mutation is a congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis.

MalaCards based summary: Lissencephaly 3, also known as lissencephaly due to tuba1a mutation, is related to lissencephaly 2 and lissencephaly type 3-familial fetal akinesia sequence syndrome, and has symptoms including ataxia and seizures. An important gene associated with Lissencephaly 3 is TUBA1A (Tubulin Alpha 1a), and among its related pathways/superpathways are Development Slit-Robo signaling and Neurogenesis regulation in the olfactory epithelium. Affiliated tissues include brain and cerebellum, and related phenotypes are agenesis of corpus callosum and microcephaly

UniProtKB/Swiss-Prot: 73 A classic type lissencephaly associated with psychomotor retardation and seizures. Features include agyria or pachygyria or laminar heterotopia, severe intellectual disability, motor delay, variable presence of seizures, and abnormalities of corpus callosum, hippocampus, cerebellar vermis and brainstem.

Disease Ontology: 11 A lissencephaly characterized by brain malformations, microcephaly, developmental delay and epilepsy that has material basis in heterozygous mutation in TUBA1A on chromosome 12q13.12.

More information from OMIM: 611603 PS607432

Related Diseases for Lissencephaly 3

Graphical network of the top 20 diseases related to Lissencephaly 3:



Diseases related to Lissencephaly 3

Symptoms & Phenotypes for Lissencephaly 3

Human phenotypes related to Lissencephaly 3:

58 30 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 58 30 Frequent (79-30%)
HP:0001274
2 microcephaly 58 30 Frequent (79-30%)
HP:0000252
3 ventriculomegaly 58 30 Very frequent (99-80%)
HP:0002119
4 polymicrogyria 58 30 Occasional (29-5%)
HP:0002126
5 pachygyria 58 30 Occasional (29-5%)
HP:0001302
6 cerebellar vermis hypoplasia 58 30 Frequent (79-30%)
HP:0001320
7 hypoplasia of the corpus callosum 58 30 Frequent (79-30%)
HP:0002079
8 hypoplasia of the brainstem 58 30 Frequent (79-30%)
HP:0002365
9 agyria 58 30 Occasional (29-5%)
HP:0031882
10 seizure 30 HP:0001250
11 spasticity 58 Frequent (79-30%)
12 nystagmus 58 Occasional (29-5%)
13 ataxia 30 HP:0001251
14 hypotonia 58 Frequent (79-30%)
15 global developmental delay 58 Very frequent (99-80%)
16 spastic tetraplegia 30 HP:0002510
17 intellectual disability, severe 30 HP:0010864
18 strabismus 58 Frequent (79-30%)
19 motor delay 30 HP:0001270
20 aganglionic megacolon 58 Very rare (<4-1%)
21 microretrognathia 58 Frequent (79-30%)
22 partial agenesis of the corpus callosum 58 Occasional (29-5%)
23 infantile spasms 58 Occasional (29-5%)
24 bilateral tonic-clonic seizure 58 Frequent (79-30%)
25 lissencephaly 58 Frequent (79-30%)
26 gray matter heterotopia 30 HP:0002282
27 generalized hypotonia 30 HP:0001290
28 focal-onset seizure 58 Occasional (29-5%)
29 optic nerve hypoplasia 58 Occasional (29-5%)
30 dysplastic corpus callosum 58 Occasional (29-5%)
31 dilated fourth ventricle 58 Frequent (79-30%)
32 hypoplastic hippocampus 58 Occasional (29-5%)
33 dysgenesis of the hippocampus 58 Frequent (79-30%)
34 perisylvian polymicrogyria 58 Occasional (29-5%)
35 dysgenesis of the basal ganglia 58 Very frequent (99-80%)
36 hypoplastic anterior limbs of the internal capsule 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
ataxia
hypotonia
spastic tetraplegia
polymicrogyria
lissencephaly
more
Head And Neck Head:
microcephaly

Clinical features from OMIM®:

611603 (Updated 08-Dec-2022)

UMLS symptoms related to Lissencephaly 3:


ataxia; seizures

MGI Mouse Phenotypes related to Lissencephaly 3:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.28 ACTR3B ARPC5L CENPJ DAB1 NCAM2 PAFAH1B1

Drugs & Therapeutics for Lissencephaly 3

Search Clinical Trials, NIH Clinical Center for Lissencephaly 3

Cochrane evidence based reviews: lissencephaly 3

Genetic Tests for Lissencephaly 3

Genetic tests related to Lissencephaly 3:

# Genetic test Affiliating Genes
1 Lissencephaly Due to Tuba1a Mutation 28 TUBA1A
2 Lissencephaly Type 3 28

Anatomical Context for Lissencephaly 3

Organs/tissues related to Lissencephaly 3:

MalaCards : Brain, Cerebellum
ODiseA: Brain

Publications for Lissencephaly 3

Articles related to Lissencephaly 3:

(show all 20)
# Title Authors PMID Year
1
TUBA1A mutations: from isolated lissencephaly to familial polymicrogyria. 57 5
21403111 2011
2
TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins. 57 5
20466733 2010
3
Refining the phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly. 57 5
18954413 2008
4
Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations. 57 5
18728072 2008
5
Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A). 57 5
17584854 2007
6
Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. 57 5
17218254 2007
7
Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants. 5
34906502 2022
8
Genetic heterogeneity of polymicrogyria: study of 123 patients using deep sequencing. 5
33604570 2021
9
TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity. 5
30517687 2019
10
The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy. 5
30744660 2019
11
Comprehensive genomic analysis of patients with disorders of cerebral cortical development. 5
29706646 2018
12
Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation. 5
30087272 2018
13
Molecular diagnostic experience of whole-exome sequencing in adult patients. 5
26633545 2016
14
Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly. 57
25059107 2014
15
The wide spectrum of tubulinopathies: what are the key features for the diagnosis? 5
24860126 2014
16
Expanding the spectrum of TUBA1A-related cortical dysgenesis to Polymicrogyria. 57
22948023 2013
17
Disease-associated mutations in TUBA1A result in a spectrum of defects in the tubulin folding and heterodimer assembly pathway. 5
20603323 2010
18
Neuropathological phenotype of a distinct form of lissencephaly associated with mutations in TUBA1A. 5
18669490 2008
19
Iterative ACORN as a high throughput tool in structural genomics. 62
17133764 2006
20
Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration. 62
7751941 1995

Variations for Lissencephaly 3

ClinVar genetic disease variations for Lissencephaly 3:

5 (show top 50) (show all 92)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CENPJ NM_018451.5(CENPJ):c.1132C>T (p.Arg378Ter) SNV Pathogenic
503611 rs201111299 GRCh37: 13:25481044-25481044
GRCh38: 13:24906906-24906906
2 CENPJ NM_018451.5(CENPJ):c.289dup (p.Thr97fs) DUP Pathogenic
279750 rs759188041 GRCh37: 13:25486874-25486875
GRCh38: 13:24912736-24912737
3 TUBA1A NM_006009.4(TUBA1A):c.701T>G (p.Ile234Ser) SNV Pathogenic
976320 rs1942171599 GRCh37: 12:49579448-49579448
GRCh38: 12:49185665-49185665
4 TUBA1A NM_006009.4(TUBA1A):c.545T>C (p.Val182Ala) SNV Pathogenic
977324 rs1942173367 GRCh37: 12:49579604-49579604
GRCh38: 12:49185821-49185821
5 TUBA1A NM_006009.4(TUBA1A):c.431G>T (p.Gly144Val) SNV Pathogenic
1164064 GRCh37: 12:49579718-49579718
GRCh38: 12:49185935-49185935
6 TUBA1A NM_006009.4(TUBA1A):c.26T>C (p.Val9Ala) SNV Pathogenic
625491 rs1565627795 GRCh37: 12:49580594-49580594
GRCh38: 12:49186811-49186811
7 TUBA1A NM_006009.4(TUBA1A):c.1288_1302del (p.Lys430_Glu434del) DEL Pathogenic
1065497 GRCh37: 12:49578847-49578861
GRCh38: 12:49185064-49185078
8 TUBA1A NM_006009.4(TUBA1A):c.790C>T (p.Arg264Cys) SNV Pathogenic
7070 rs137853043 GRCh37: 12:49579359-49579359
GRCh38: 12:49185576-49185576
9 TUBA1A NM_006009.4(TUBA1A):c.1205G>A (p.Arg402His) SNV Pathogenic
7071 rs137853044 GRCh37: 12:49578944-49578944
GRCh38: 12:49185161-49185161
10 TUBA1A NM_006009.4(TUBA1A):c.562A>C (p.Ile188Leu) SNV Pathogenic
7072 rs137853045 GRCh37: 12:49579587-49579587
GRCh38: 12:49185804-49185804
11 TUBA1A NM_006009.4(TUBA1A):c.787C>A (p.Pro263Thr) SNV Pathogenic
7073 rs137853046 GRCh37: 12:49579362-49579362
GRCh38: 12:49185579-49185579
12 TUBA1A NM_006009.4(TUBA1A):c.1256C>T (p.Ser419Leu) SNV Pathogenic
7074 rs137853047 GRCh37: 12:49578893-49578893
GRCh38: 12:49185110-49185110
13 TUBA1A NM_006009.4(TUBA1A):c.1190T>C (p.Leu397Pro) SNV Pathogenic
7075 rs137853048 GRCh37: 12:49578959-49578959
GRCh38: 12:49185176-49185176
14 TUBA1A NM_006009.4(TUBA1A):c.1264C>T (p.Arg422Cys) SNV Pathogenic
7076 rs137853049 GRCh37: 12:49578885-49578885
GRCh38: 12:49185102-49185102
15 TUBA1A NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His) SNV Pathogenic
7077 rs137853050 GRCh37: 12:49578884-49578884
GRCh38: 12:49185101-49185101
16 TUBA1A NM_006009.4(TUBA1A):c.13A>C (p.Ile5Leu) SNV Pathogenic
30268 rs387906840 GRCh37: 12:49580607-49580607
GRCh38: 12:49186824-49186824
17 TUBA1A NM_006009.4(TUBA1A):c.1204C>T (p.Arg402Cys) SNV Pathogenic
160146 rs587784483 GRCh37: 12:49578945-49578945
GRCh38: 12:49185162-49185162
18 TUBA1A NM_006009.4(TUBA1A):c.1205G>T (p.Arg402Leu) SNV Pathogenic
160147 rs137853044 GRCh37: 12:49578944-49578944
GRCh38: 12:49185161-49185161
19 TUBA1A NM_006009.4(TUBA1A):c.958C>T (p.Arg320Cys) SNV Pathogenic
864866 rs1942168488 GRCh37: 12:49579191-49579191
GRCh38: 12:49185408-49185408
20 TUBA1A NM_006009.4(TUBA1A):c.481T>G (p.Tyr161Asp) SNV Pathogenic
160158 rs587784488 GRCh37: 12:49579668-49579668
GRCh38: 12:49185885-49185885
21 TUBA1A NM_006009.4(TUBA1A):c.986A>G (p.Asn329Ser) SNV Pathogenic
160167 rs587784495 GRCh37: 12:49579163-49579163
GRCh38: 12:49185380-49185380
22 TUBA1A NM_006009.4(TUBA1A):c.1226T>C (p.Val409Ala) SNV Pathogenic
208490 rs797045005 GRCh37: 12:49578923-49578923
GRCh38: 12:49185140-49185140
23 TUBA1A NM_006009.4(TUBA1A):c.1224C>A (p.Tyr408Ter) SNV Pathogenic
209200 rs753719501 GRCh37: 12:49578925-49578925
GRCh38: 12:49185142-49185142
24 TUBA1A NM_006009.4(TUBA1A):c.1169G>A (p.Arg390His) SNV Pathogenic
488628 rs1064796460 GRCh37: 12:49578980-49578980
GRCh38: 12:49185197-49185197
25 TUBA1A NM_006009.4(TUBA1A):c.652G>A (p.Asp218Asn) SNV Pathogenic
Likely Pathogenic
372561 rs1057517858 GRCh37: 12:49579497-49579497
GRCh38: 12:49185714-49185714
26 TUBA1A NM_006009.4(TUBA1A):c.167C>T (p.Thr56Met) SNV Pathogenic
625513 rs1565627727 GRCh37: 12:49580453-49580453
GRCh38: 12:49186670-49186670
27 TUBA1A NM_006009.4(TUBA1A):c.53A>G (p.Asn18Ser) SNV Pathogenic
421567 rs1064795213 GRCh37: 12:49580567-49580567
GRCh38: 12:49186784-49186784
28 TUBA1A NM_006009.4(TUBA1A):c.518C>T (p.Pro173Leu) SNV Pathogenic
625511 rs1565627304 GRCh37: 12:49579631-49579631
GRCh38: 12:49185848-49185848
29 TUBA1A NM_006009.4(TUBA1A):c.1169G>C (p.Arg390Pro) SNV Pathogenic/Likely Pathogenic
423490 rs1064796460 GRCh37: 12:49578980-49578980
GRCh38: 12:49185197-49185197
30 TUBA1A NM_006009.4(TUBA1A):c.352G>A (p.Val118Met) SNV Pathogenic/Likely Pathogenic
217023 rs863224938 GRCh37: 12:49580116-49580116
GRCh38: 12:49186333-49186333
31 TUBA1A NM_006009.4(TUBA1A):c.1105G>A (p.Ala369Thr) SNV Pathogenic/Likely Pathogenic
212488 rs797046071 GRCh37: 12:49579044-49579044
GRCh38: 12:49185261-49185261
32 TUBA1A NM_006009.4(TUBA1A):c.641G>A (p.Arg214His) SNV Pathogenic/Likely Pathogenic
372542 rs1057517843 GRCh37: 12:49579508-49579508
GRCh38: 12:49185725-49185725
33 TUBA1A NM_006009.4(TUBA1A):c.5G>A (p.Arg2His) SNV Pathogenic/Likely Pathogenic
160161 rs587784491 GRCh37: 12:49580615-49580615
GRCh38: 12:49186832-49186832
34 TUBA1A NM_006009.4(TUBA1A):c.698A>G (p.Gln233Arg) SNV Likely Pathogenic
160162 rs587784492 GRCh37: 12:49579451-49579451
GRCh38: 12:49185668-49185668
35 TUBA1A NM_006009.4(TUBA1A):c.808G>T (p.Ala270Ser) SNV Likely Pathogenic
160164 rs587784494 GRCh37: 12:49579341-49579341
GRCh38: 12:49185558-49185558
36 TUBA1A NM_006009.4(TUBA1A):c.995T>C (p.Ile332Thr) SNV Likely Pathogenic
160169 rs587784497 GRCh37: 12:49579154-49579154
GRCh38: 12:49185371-49185371
37 TUBA1A NM_006009.4(TUBA1A):c.521C>T (p.Ala174Val) SNV Likely Pathogenic
160159 rs587784489 GRCh37: 12:49579628-49579628
GRCh38: 12:49185845-49185845
38 TUBA1A NM_006009.4(TUBA1A):c.1144A>G (p.Thr382Ala) SNV Likely Pathogenic
437121 rs1555162294 GRCh37: 12:49579005-49579005
GRCh38: 12:49185222-49185222
39 TUBA1A NM_006009.4(TUBA1A):c.368G>A (p.Arg123His) SNV Likely Pathogenic
437122 rs1555162456 GRCh37: 12:49580100-49580100
GRCh38: 12:49186317-49186317
40 TUBA1A NM_006009.4(TUBA1A):c.1304T>C (p.Val435Ala) SNV Likely Pathogenic
437120 rs1555162242 GRCh37: 12:49578845-49578845
GRCh38: 12:49185062-49185062
41 TUBA1A NM_006009.4(TUBA1A):c.970G>C (p.Val324Leu) SNV Likely Pathogenic
212494 rs797046073 GRCh37: 12:49579179-49579179
GRCh38: 12:49185396-49185396
42 TUBA1A NM_006009.4(TUBA1A):c.269A>G (p.Glu90Gly) SNV Likely Pathogenic
212491 rs797046072 GRCh37: 12:49580199-49580199
GRCh38: 12:49186416-49186416
43 TUBA1A NM_006009.4(TUBA1A):c.1274T>A (p.Met425Lys) SNV Likely Pathogenic
160148 rs587784484 GRCh37: 12:49578875-49578875
GRCh38: 12:49185092-49185092
44 TUBA1A NM_006009.4(TUBA1A):c.152C>T (p.Thr51Ile) SNV Likely Pathogenic
160149 rs587784485 GRCh37: 12:49580468-49580468
GRCh38: 12:49186685-49186685
45 TUBA1A NM_006009.4(TUBA1A):c.162T>A (p.Ser54Arg) SNV Likely Pathogenic
160150 rs587784486 GRCh37: 12:49580458-49580458
GRCh38: 12:49186675-49186675
46 TUBA1A NM_006009.4(TUBA1A):c.703G>C (p.Val235Leu) SNV Likely Pathogenic
1028472 rs1565627190 GRCh37: 12:49579446-49579446
GRCh38: 12:49185663-49185663
47 TUBA1A NM_006009.4(TUBA1A):c.3+3del DEL Likely Pathogenic
1064595 GRCh37: 12:49582757-49582757
GRCh38: 12:49188974-49188974
48 TUBA1A NM_006009.4(TUBA1A):c.879_899del (p.Ala294_Asn300del) DEL Likely Pathogenic
1705279 GRCh37: 12:49579250-49579270
GRCh38: 12:49185467-49185487
49 TUBA1A NM_006009.4(TUBA1A):c.635_640del (p.Ile212_Arg214delinsSer) DEL Likely Pathogenic
1679172 GRCh37: 12:49579509-49579514
GRCh38: 12:49185726-49185731
50 TUBA1A NM_006009.4(TUBA1A):c.1129A>G (p.Met377Val) SNV Likely Pathogenic
160142 rs587784481 GRCh37: 12:49579020-49579020
GRCh38: 12:49185237-49185237

UniProtKB/Swiss-Prot genetic disease variations for Lissencephaly 3:

73
# Symbol AA change Variation ID SNP ID
1 TUBA1A p.Ile188Leu VAR_039332 rs137853045
2 TUBA1A p.Pro263Thr VAR_039333 rs137853046
3 TUBA1A p.Arg264Cys VAR_039334 rs137853043
4 TUBA1A p.Leu286Phe VAR_039335
5 TUBA1A p.Arg402Cys VAR_039336 rs587784483
6 TUBA1A p.Arg402His VAR_039337 rs137853044
7 TUBA1A p.Ser419Leu VAR_039338 rs137853047
8 TUBA1A p.Arg402Leu VAR_078711 rs137853044

Expression for Lissencephaly 3

Search GEO for disease gene expression data for Lissencephaly 3.

Pathways for Lissencephaly 3

Pathways related to Lissencephaly 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.63 TUBA1A ARPC5L ACTR3B
2 11.01 PAFAH1B1 DAB1
3 10.4 PAFAH1B1 DAB1
4 10.07 PAFAH1B1 DAB1

GO Terms for Lissencephaly 3

Biological processes related to Lissencephaly 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule-based process GO:0007017 9.56 TUBA1A PAFAH1B1
2 neuron migration GO:0001764 9.46 TUBA1A PAFAH1B1 DAB1
3 microtubule polymerization GO:0046785 9.13 TUBA1A CENPJ
4 radial glia-guided pyramidal neuron migration GO:0140650 8.92 PAFAH1B1 DAB1

Sources for Lissencephaly 3

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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