LIS8
MCID: LSS035
MIFTS: 35

Lissencephaly 8 (LIS8)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Lissencephaly 8

MalaCards integrated aliases for Lissencephaly 8:

Name: Lissencephaly 8 57 11 73 28 5 14 38
Lis8 57 11 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy


Classifications:



Summaries for Lissencephaly 8

OMIM®: 57 Lissencephaly-8 (LIS8) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, and hypotonia. Brain imaging shows variable features, including cortical gyral abnormalities and hypoplasia of the corpus callosum, brainstem, and cerebellum (Jerber et al., 2016). For a general description and a discussion of genetic heterogeneity lissencephaly, see LIS1 (607432). (617255) (Updated 08-Dec-2022)

MalaCards based summary: Lissencephaly 8, also known as lis8, is related to epilepsy, idiopathic generalized 14 and schuurs-hoeijmakers syndrome. An important gene associated with Lissencephaly 8 is TMTC3 (Transmembrane O-Mannosyltransferase Targeting Cadherins 3), and among its related pathways/superpathways are Vesicle-mediated transport and Rab regulation of trafficking. Affiliated tissues include cerebellum, cortex and brain, and related phenotypes are intellectual disability and seizure

UniProtKB/Swiss-Prot: 73 A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS8 patients manifest delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, hypotonia, cortical gyral abnormalities, and hypoplasia of the corpus callosum, brainstem and cerebellum. LIS8 inheritance is autosomal recessive.

Disease Ontology: 11 A lissencephaly characterized by delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, and hypotonia that has material basis in homozygous or compound heterozygous mutation in TMTC3 on chromosome 12q21.32.

Related Diseases for Lissencephaly 8

Symptoms & Phenotypes for Lissencephaly 8

Human phenotypes related to Lissencephaly 8:

30 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 30 Very rare (1%) HP:0001249
2 seizure 30 Very rare (1%) HP:0001250
3 cataract 30 Very rare (1%) HP:0000518
4 global developmental delay 30 Very rare (1%) HP:0001263
5 microcephaly 30 Very rare (1%) HP:0000252
6 optic atrophy 30 Very rare (1%) HP:0000648
7 absent speech 30 Very rare (1%) HP:0001344
8 delayed social development 30 Very rare (1%) HP:0012434
9 elevated circulating creatine kinase concentration 30 Very rare (1%) HP:0003236
10 talipes equinovarus 30 Very rare (1%) HP:0001762
11 microphthalmia 30 Very rare (1%) HP:0000568
12 ventriculomegaly 30 Very rare (1%) HP:0002119
13 polymicrogyria 30 Very rare (1%) HP:0002126
14 cerebellar hypoplasia 30 Very rare (1%) HP:0001321
15 autistic behavior 30 Very rare (1%) HP:0000729
16 occipital encephalocele 30 Very rare (1%) HP:0002085
17 hypoplasia of the corpus callosum 30 Very rare (1%) HP:0002079
18 retrocerebellar cyst 30 Very rare (1%) HP:0006951
19 type ii lissencephaly 30 Very rare (1%) HP:0007260
20 cerebral hypomyelination 30 Very rare (1%) HP:0006808
21 hypoplasia of the brainstem 30 Very rare (1%) HP:0002365
22 agyria 30 Very rare (1%) HP:0031882
23 delayed fine motor development 30 Very rare (1%) HP:0010862
24 axial hypotonia 30 Very rare (1%) HP:0008936
25 appendicular spasticity 30 Very rare (1%) HP:0034353
26 delayed ability to walk 30 HP:0031936

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
intellectual disability
ventriculomegaly
polymicrogyria
hypoplasia of the corpus callosum
hypoplasia of the brainstem
more
Head And Neck Head:
microcephaly (in some patients)

Muscle Soft Tissue:
truncal hypotonia
no muscle atrophy

Laboratory Abnormalities:
increased serum creatine kinase (rare)

Skeletal Feet:
club feet (in some patients)

Head And Neck Eyes:
cataracts (in some patients)
ophthalmologic abnormalities are rare
optic atrophy (in 1 patient)

Neurologic Behavioral Psychiatric Manifestations:
autistic features (in some patients)

Clinical features from OMIM®:

617255 (Updated 08-Dec-2022)

Drugs & Therapeutics for Lissencephaly 8

Search Clinical Trials, NIH Clinical Center for Lissencephaly 8

Genetic Tests for Lissencephaly 8

Genetic tests related to Lissencephaly 8:

# Genetic test Affiliating Genes
1 Lissencephaly 8 28 TMTC3

Anatomical Context for Lissencephaly 8

Organs/tissues related to Lissencephaly 8:

MalaCards : Cerebellum, Cortex, Brain
ODiseA: Brain

Publications for Lissencephaly 8

Articles related to Lissencephaly 8:

# Title Authors PMID Year
1
Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. 57 5
27773428 2016
2
Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders. 5
28097321 2017
3
The evaluation of hospital laboratory information management systems based on the standards of the American National Standard Institute. 62
25077154 2014

Variations for Lissencephaly 8

ClinVar genetic disease variations for Lissencephaly 8:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TMTC3 NM_181783.4(TMTC3):c.1462del (p.Arg488fs) DEL Pathogenic
372273 rs1057517696 GRCh37: 12:88582648-88582648
GRCh38: 12:88188871-88188871
2 TMTC3 NM_181783.4(TMTC3):c.2617C>T (p.Gln873Ter) SNV Pathogenic
372274 rs1057517697 GRCh37: 12:88589298-88589298
GRCh38: 12:88195521-88195521
3 TMTC3 NM_181783.4(TMTC3):c.3G>A (p.Met1Ile) SNV Pathogenic
372277 rs1057517698 GRCh37: 12:88542095-88542095
GRCh38: 12:88148318-88148318
4 TMTC3 NM_181783.4(TMTC3):c.1959_1960insTT (p.Arg654fs) INSERT Pathogenic
372275 rs1057519417 GRCh37: 12:88588639-88588640
GRCh38: 12:88194862-88194863
5 TMTC3 NM_181783.4(TMTC3):c.199C>G (p.His67Asp) SNV Pathogenic/Likely Pathogenic
372276 rs754200057 GRCh37: 12:88547077-88547077
GRCh38: 12:88153300-88153300
6 TMTC3 NM_181783.4(TMTC3):c.747TGT[1] (p.Val251del) MICROSAT Likely Pathogenic
1319671 GRCh37: 12:88554577-88554579
GRCh38: 12:88160800-88160802
7 TMTC3 NM_181783.4(TMTC3):c.1554del (p.Lys518fs) DEL Likely Pathogenic
1339495 GRCh37: 12:88584242-88584242
GRCh38: 12:88190465-88190465
8 TMTC3 NM_181783.4(TMTC3):c.10A>G (p.Ile4Val) SNV Uncertain Significance
1033238 rs146954242 GRCh37: 12:88542102-88542102
GRCh38: 12:88148325-88148325
9 TMTC3 NM_181783.4(TMTC3):c.816T>A (p.Ala272=) SNV Uncertain Significance
1033240 rs1250204793 GRCh37: 12:88560125-88560125
GRCh38: 12:88166348-88166348

UniProtKB/Swiss-Prot genetic disease variations for Lissencephaly 8:

73
# Symbol AA change Variation ID SNP ID
1 TMTC3 p.His67Asp VAR_077900
2 TMTC3 p.Gly384Glu VAR_077901

Expression for Lissencephaly 8

Search GEO for disease gene expression data for Lissencephaly 8.

Pathways for Lissencephaly 8

Pathways related to Lissencephaly 8 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.67 NECAP2 NECAP1 DENND5B DENND5A DENND4C
2
Show member pathways
11.55 DENND5B DENND5A DENND4C
3 10.25 CSNK1G3 CSNK1G2

GO Terms for Lissencephaly 8

Cellular components related to Lissencephaly 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 clathrin-coated vesicle membrane GO:0030665 9.16 NECAP2 NECAP1
2 retromer complex GO:0030904 9.13 DENND5A DENND4C
3 clathrin vesicle coat GO:0030125 8.92 NECAP2 NECAP1

Biological processes related to Lissencephaly 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endocytosis GO:0006897 9.17 NECAP2 NECAP1 CSNK1G3 CSNK1G2

Molecular functions related to Lissencephaly 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mannosyltransferase activity GO:0000030 8.92 TMTC3 PIGB

Sources for Lissencephaly 8

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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