MSCCA
MCID: MCR355
MIFTS: 34

Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy (MSCCA)

Categories: Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Microcephaly, Progressive, with Seizures and Cerebral and...

MalaCards integrated aliases for Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

Name: Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy 57 72 29 6 70
Microcephaly, Progressive, Seizures, and Cerebral and Cerebellar Atrophy 57 39
Mscca 57 72
Diffuse Cerebral and Cerebellar Atrophy-Intractable Seizures-Progressive Microcephaly Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset at birth or early infancy
dysmorphic features are variable
two unrelated families have been reported (last curated april 2014)


HPO:

31
microcephaly, progressive, with seizures and cerebral and cerebellar atrophy:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Microcephaly, Progressive, with Seizures and Cerebral and...

UniProtKB/Swiss-Prot : 72 Microcephaly, progressive, with seizures and cerebral and cerebellar atrophy: A severe, autosomal recessive, neurodevelopmental and neurodegenerative disorder characterized by progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, resulting in profoundly delayed development and hypotonia.

MalaCards based summary : Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy, is also known as microcephaly, progressive, seizures, and cerebral and cerebellar atrophy. An important gene associated with Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy is QARS1 (Glutaminyl-TRNA Synthetase 1), and among its related pathways/superpathways is tRNA Aminoacylation. Affiliated tissues include cortex, brain and prostate, and related phenotypes are hyperreflexia and simplified gyral pattern

OMIM® : 57 Progressive microcephaly with seizures and cerebral and cerebellar atrophy is a severe autosomal recessive neurodevelopmental and neurodegenerative disorder with onset in the first days or months of life. Patients are born with microcephaly and soon develop intractable seizures, resulting in profoundly delayed development and hypotonia (summary by Zhang et al., 2014). (615760) (Updated 05-Apr-2021)

Related Diseases for Microcephaly, Progressive, with Seizures and Cerebral and...

Symptoms & Phenotypes for Microcephaly, Progressive, with Seizures and Cerebral and...

Human phenotypes related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hyperreflexia 31 occasional (7.5%) HP:0001347
2 simplified gyral pattern 31 occasional (7.5%) HP:0009879
3 global developmental delay 31 HP:0001263
4 microcephaly 31 HP:0000252
5 low-set ears 31 HP:0000369
6 epicanthus 31 HP:0000286
7 ventriculomegaly 31 HP:0002119
8 hypotelorism 31 HP:0000601
9 sloping forehead 31 HP:0000340
10 hypoplasia of the corpus callosum 31 HP:0002079
11 status epilepticus 31 HP:0002133
12 posteriorly rotated ears 31 HP:0000358
13 cerebral atrophy 31 HP:0002059
14 generalized hypotonia 31 HP:0001290
15 cerebellar vermis atrophy 31 HP:0006855
16 narrow forehead 31 HP:0000341
17 cns hypomyelination 31 HP:0003429
18 progressive microcephaly 31 HP:0000253

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Head And Neck Head:
sloping forehead
bitemporal narrowing
microcephaly, progressive (-3 to -10 sd)

Muscle Soft Tissue:
hypotonia

Head And Neck Eyes:
hypotelorism
epicanthal folds
lack of visual contact

Neurologic Central Nervous System:
status epilepticus
cerebral atrophy
hypotonia
enlarged ventricles
hypomyelination
more
Head And Neck Nose:
broad, flat nasal bridge

Clinical features from OMIM®:

615760 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Negative genetic interaction between MUS81-/- and MUS81+/+ GR00255-A-2 8.62 EPRS1 QARS1

Drugs & Therapeutics for Microcephaly, Progressive, with Seizures and Cerebral and...

Search Clinical Trials , NIH Clinical Center for Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy

Genetic Tests for Microcephaly, Progressive, with Seizures and Cerebral and...

Genetic tests related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

# Genetic test Affiliating Genes
1 Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy 29 QARS1

Anatomical Context for Microcephaly, Progressive, with Seizures and Cerebral and...

MalaCards organs/tissues related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

40
Cortex, Brain, Prostate

Publications for Microcephaly, Progressive, with Seizures and Cerebral and...

Articles related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

(show all 13)
# Title Authors PMID Year
1
Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. 6 57
24656866 2014
2
The crystal structure of human GlnRS provides basis for the development of neurological disorders. 6
26869582 2016
3
Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities. 6
25432320 2015
4
Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy. 6
25471517 2015
5
A single-center 10-year retrospective study of clinical features and surgical treatment of spinal metastasis from cholangiocarcinoma. 61
33353354 2021
6
Inter- and Intra-Subject Transfer Reduces Calibration Effort for High-Speed SSVEP-Based BCIs. 61
32841119 2020
7
Surgical Margins: The Perspective of Pathology. 61
28709535 2017
8
Single mechanosensitive and Ca²⁺-sensitive channel currents recorded from mouse and human embryonic stem cells. 61
23188062 2013
9
Mechanosensitive Ca(2+) permeant cation channels in human prostate tumor cells. 61
22874798 2012
10
Revisiting TRPC1 and TRPC6 mechanosensitivity. 61
17957383 2008
11
MscCa Regulation of Tumor Cell Migration and Metastasis. 61
25168147 2007
12
Mechanosensitive channels in neurite outgrowth. 61
25168135 2007
13
TRPC1 forms the stretch-activated cation channel in vertebrate cells. 61
15665854 2005

Variations for Microcephaly, Progressive, with Seizures and Cerebral and...

ClinVar genetic disease variations for Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

6 (show top 50) (show all 215)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 QARS1 NM_005051.3(QARS1):c.134G>T (p.Gly45Val) SNV Pathogenic 127115 rs587777331 GRCh37: 3:49141888-49141888
GRCh38: 3:49104455-49104455
2 QARS1 NM_005051.3(QARS1):c.169T>C (p.Tyr57His) SNV Pathogenic 127117 rs587777333 GRCh37: 3:49141853-49141853
GRCh38: 3:49104420-49104420
3 QARS1 NM_005051.3(QARS1):c.1543C>T (p.Arg515Trp) SNV Pathogenic 127118 rs587777334 GRCh37: 3:49136848-49136848
GRCh38: 3:49099415-49099415
4 QARS1 NM_005051.3(QARS1):c.1387C>T (p.Arg463Ter) SNV Pathogenic 477827 rs755674457 GRCh37: 3:49137195-49137195
GRCh38: 3:49099762-49099762
5 QARS1 NM_005051.3(QARS1):c.585del (p.Arg195_Leu196insTer) Deletion Pathogenic 477841 rs1241706645 GRCh37: 3:49139684-49139684
GRCh38: 3:49102251-49102251
6 QARS1 NM_005051.3(QARS1):c.1284_1285del (p.Asp430fs) Deletion Pathogenic 544132 rs775652214 GRCh37: 3:49137404-49137405
GRCh38: 3:49099971-49099972
7 QARS1 NM_005051.3(QARS1):c.1612del (p.Arg538fs) Deletion Pathogenic 544142 rs1553751717 GRCh37: 3:49136779-49136779
GRCh38: 3:49099346-49099346
8 QARS1 NM_005051.3(QARS1):c.1567C>T (p.Arg523Ter) SNV Pathogenic 566178 rs767667312 GRCh37: 3:49136824-49136824
GRCh38: 3:49099391-49099391
9 QARS1 NM_005051.3(QARS1):c.1058G>T (p.Gly353Val) SNV Pathogenic 828125 rs752600100 GRCh37: 3:49137729-49137729
GRCh38: 3:49100296-49100296
10 QARS1 NM_005051.3(QARS1):c.387_390dup (p.Asn131delinsTyrTer) Duplication Pathogenic 997652 GRCh37: 3:49141124-49141125
GRCh38: 3:49103691-49103692
11 QARS1 NM_005051.3(QARS1):c.1689_1690CA[1] (p.Thr564fs) Microsatellite Pathogenic 580993 rs1559966797 GRCh37: 3:49136609-49136610
GRCh38: 3:49099176-49099177
12 QARS1 NM_005051.3(QARS1):c.1009_1012del (p.Asp337fs) Deletion Pathogenic 863518 GRCh37: 3:49137856-49137859
GRCh38: 3:49100423-49100426
13 QARS1 NM_005051.3(QARS1):c.1081C>T (p.Arg361Ter) SNV Pathogenic 941594 GRCh37: 3:49137706-49137706
GRCh38: 3:49100273-49100273
14 QARS1 NM_005051.3(QARS1):c.425dup (p.Tyr142Ter) Duplication Pathogenic 957907 GRCh37: 3:49141089-49141090
GRCh38: 3:49103656-49103657
15 QARS1 NM_005051.3(QARS1):c.256del (p.Gln86fs) Deletion Pathogenic 965194 GRCh37: 3:49141766-49141766
GRCh38: 3:49104333-49104333
16 QARS1 NM_005051.3(QARS1):c.1699C>T (p.Arg567Ter) SNV Pathogenic 860157 GRCh37: 3:49136602-49136602
GRCh38: 3:49099169-49099169
17 QARS1 NM_005051.3(QARS1):c.851_852insGC (p.Ile284fs) Insertion Pathogenic 1034152 GRCh37: 3:49138812-49138813
GRCh38: 3:49101379-49101380
18 QARS1 NM_005051.3(QARS1):c.477G>A (p.Trp159Ter) SNV Pathogenic/Likely pathogenic 984949 GRCh37: 3:49140817-49140817
GRCh38: 3:49103384-49103384
19 QARS1 NM_005051.3(QARS1):c.2085-3C>A SNV Likely pathogenic 634571 rs1024765171 GRCh37: 3:49135694-49135694
GRCh38: 3:49098261-49098261
20 QARS1 NM_005051.3(QARS1):c.1615-2A>T SNV Likely pathogenic 936875 GRCh37: 3:49136688-49136688
GRCh38: 3:49099255-49099255
21 QARS1 NM_005051.3(QARS1):c.789+1G>T SNV Likely pathogenic 846851 GRCh37: 3:49139052-49139052
GRCh38: 3:49101619-49101619
22 QARS1 NM_005051.3(QARS1):c.1207C>T (p.Arg403Trp) SNV Conflicting interpretations of pathogenicity 127116 rs587777332 GRCh37: 3:49137482-49137482
GRCh38: 3:49100049-49100049
23 QARS1 NM_005051.3(QARS1):c.297G>C (p.Leu99Phe) SNV Uncertain significance 426951 rs147794116 GRCh37: 3:49141374-49141374
GRCh38: 3:49103941-49103941
24 QARS1 NM_005051.3(QARS1):c.1832T>G (p.Ile611Ser) SNV Uncertain significance 477834 rs757743183 GRCh37: 3:49136349-49136349
GRCh38: 3:49098916-49098916
25 QARS1 NM_005051.3(QARS1):c.1388G>A (p.Arg463Gln) SNV Uncertain significance 544131 rs374178767 GRCh37: 3:49137194-49137194
GRCh38: 3:49099761-49099761
26 QARS1 NM_005051.3(QARS1):c.1195G>A (p.Glu399Lys) SNV Uncertain significance 544138 rs143072084 GRCh37: 3:49137494-49137494
GRCh38: 3:49100061-49100061
27 QARS1 NM_005051.3(QARS1):c.1246G>A (p.Val416Ile) SNV Uncertain significance 449755 rs147076980 GRCh37: 3:49137443-49137443
GRCh38: 3:49100010-49100010
28 QARS1 NM_005051.3(QARS1):c.1163A>G (p.Glu388Gly) SNV Uncertain significance 567795 rs777424712 GRCh37: 3:49137624-49137624
GRCh38: 3:49100191-49100191
29 QARS1 NM_005051.3(QARS1):c.1658T>A (p.Leu553Gln) SNV Uncertain significance 571673 rs1559966841 GRCh37: 3:49136643-49136643
GRCh38: 3:49099210-49099210
30 QARS1 NM_005051.3(QARS1):c.2311G>A (p.Asp771Asn) SNV Uncertain significance 572730 rs754648501 GRCh37: 3:49133479-49133479
GRCh38: 3:49096046-49096046
31 QARS1 NM_005051.3(QARS1):c.668A>G (p.Gln223Arg) SNV Uncertain significance 578234 rs750460731 GRCh37: 3:49139296-49139296
GRCh38: 3:49101863-49101863
32 QARS1 NM_005051.3(QARS1):c.800G>A (p.Arg267Gln) SNV Uncertain significance 842521 GRCh37: 3:49138864-49138864
GRCh38: 3:49101431-49101431
33 QARS1 NM_005051.3(QARS1):c.2075A>G (p.Tyr692Cys) SNV Uncertain significance 844503 GRCh37: 3:49135795-49135795
GRCh38: 3:49098362-49098362
34 QARS1 NM_005051.3(QARS1):c.1280G>A (p.Arg427His) SNV Uncertain significance 850532 GRCh37: 3:49137409-49137409
GRCh38: 3:49099976-49099976
35 QARS1 NM_005051.3(QARS1):c.418G>C (p.Glu140Gln) SNV Uncertain significance 851630 GRCh37: 3:49141097-49141097
GRCh38: 3:49103664-49103664
36 QARS1 NM_005051.3(QARS1):c.8C>T (p.Ala3Val) SNV Uncertain significance 851800 GRCh37: 3:49142159-49142159
GRCh38: 3:49104726-49104726
37 QARS1 NM_005051.3(QARS1):c.2000G>A (p.Arg667Gln) SNV Uncertain significance 857029 GRCh37: 3:49135870-49135870
GRCh38: 3:49098437-49098437
38 QARS1 NM_005051.3(QARS1):c.2215G>A (p.Asp739Asn) SNV Uncertain significance 857235 GRCh37: 3:49135487-49135487
GRCh38: 3:49098054-49098054
39 QARS1 NM_005051.3(QARS1):c.2152G>C (p.Ala718Pro) SNV Uncertain significance 864179 GRCh37: 3:49135550-49135550
GRCh38: 3:49098117-49098117
40 QARS1 NM_005051.3(QARS1):c.143T>C (p.Ile48Thr) SNV Uncertain significance 581949 rs201397059 GRCh37: 3:49141879-49141879
GRCh38: 3:49104446-49104446
41 QARS1 NM_005051.3(QARS1):c.769C>A (p.Leu257Met) SNV Uncertain significance 583355 rs1037854666 GRCh37: 3:49139073-49139073
GRCh38: 3:49101640-49101640
42 QARS1 NM_005051.3(QARS1):c.1479T>C (p.Val493=) SNV Uncertain significance 626156 rs776640127 GRCh37: 3:49136990-49136990
GRCh38: 3:49099557-49099557
43 QARS1 NM_005051.3(QARS1):c.1741A>G (p.Asn581Asp) SNV Uncertain significance 942852 GRCh37: 3:49136560-49136560
GRCh38: 3:49099127-49099127
44 QARS1 NM_005051.3(QARS1):c.224A>G (p.Tyr75Cys) SNV Uncertain significance 942891 GRCh37: 3:49141798-49141798
GRCh38: 3:49104365-49104365
45 QARS1 NM_005051.3(QARS1):c.1309A>T (p.Thr437Ser) SNV Uncertain significance 943235 GRCh37: 3:49137273-49137273
GRCh38: 3:49099840-49099840
46 QARS1 NM_005051.3(QARS1):c.1822T>G (p.Phe608Val) SNV Uncertain significance 949381 GRCh37: 3:49136359-49136359
GRCh38: 3:49098926-49098926
47 QARS1 NM_005051.3(QARS1):c.107C>T (p.Ala36Val) SNV Uncertain significance 949601 GRCh37: 3:49142060-49142060
GRCh38: 3:49104627-49104627
48 QARS1 NM_005051.3(QARS1):c.2317G>A (p.Gly773Arg) SNV Uncertain significance 950132 GRCh37: 3:49133473-49133473
GRCh38: 3:49096040-49096040
49 QARS1 NM_005051.3(QARS1):c.214C>T (p.Leu72Phe) SNV Uncertain significance 952069 GRCh37: 3:49141808-49141808
GRCh38: 3:49104375-49104375
50 QARS1 NM_005051.3(QARS1):c.1700G>A (p.Arg567Gln) SNV Uncertain significance 952087 GRCh37: 3:49136601-49136601
GRCh38: 3:49099168-49099168

UniProtKB/Swiss-Prot genetic disease variations for Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy:

72
# Symbol AA change Variation ID SNP ID
1 QARS1 p.Gly45Val VAR_071189 rs587777331
2 QARS1 p.Tyr57His VAR_071190 rs587777333
3 QARS1 p.Arg403Trp VAR_071191 rs587777332
4 QARS1 p.Arg515Trp VAR_071192 rs587777334

Expression for Microcephaly, Progressive, with Seizures and Cerebral and...

Search GEO for disease gene expression data for Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy.

Pathways for Microcephaly, Progressive, with Seizures and Cerebral and...

Pathways related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.87 QARS1 EPRS1

GO Terms for Microcephaly, Progressive, with Seizures and Cerebral and...

Cellular components related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 aminoacyl-tRNA synthetase multienzyme complex GO:0017101 8.62 QARS1 EPRS1

Biological processes related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.16 QARS1 EPRS1
2 tRNA aminoacylation for protein translation GO:0006418 8.96 QARS1 EPRS1
3 tRNA aminoacylation GO:0043039 8.62 QARS1 EPRS1

Molecular functions related to Microcephaly, Progressive, with Seizures and Cerebral and Cerebellar Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ligase activity GO:0016874 8.96 QARS1 EPRS1
2 aminoacyl-tRNA ligase activity GO:0004812 8.62 QARS1 EPRS1

Sources for Microcephaly, Progressive, with Seizures and Cerebral and...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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