MRD22
MCID: MNT158
MIFTS: 31

Mental Retardation, Autosomal Dominant 22 (MRD22)

Categories: Ear diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mental Retardation, Autosomal Dominant 22

MalaCards integrated aliases for Mental Retardation, Autosomal Dominant 22:

Name: Mental Retardation, Autosomal Dominant 22 57 72 29 6 70
Mrd22 57 12 72
Autosomal Dominant Non-Syndromic Intellectual Disability 22 12 15
Autosomal Dominant Mental Retardation 22 12
Telomeric Deletion 1q 58
Distal Monosomy 1q 58
Distal Deletion 1q 58
Monosomy 1qter 58

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
variable expressivity
variable phenotype
incomplete penetrance of some features
two unrelated patients with a point mutation in the zbtb18 gene has been reported (last curated april 2017)
contiguous gene deletion syndrome (in most patients)

Inheritance:
autosomal dominant


HPO:

31
mental retardation, autosomal dominant 22:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0070052
OMIM® 57 612337
OMIM Phenotypic Series 57 PS156200
MeSH 44 D008607
ICD10 via Orphanet 33 Q93.5
Orphanet 58 ORPHA36367
UMLS 70 C3808184

Summaries for Mental Retardation, Autosomal Dominant 22

OMIM® : 57 MRD22 is characterized by impaired intellectual development with frequent cooccurrence of corpus callosum anomalies, hypotonia, microcephaly, growth problems, and variable facial dysmorphism (summary by van der Schoot et al., 2018). Chromosome 1q43-q44 deletion syndrome is characterized by moderate to severe mental retardation, limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures. The phenotype is variable, and not all features are observed in all patients, which may be explained in some cases by incomplete penetrance or variable expressivity (summary by Ballif et al., 2012). (612337) (Updated 05-Apr-2021)

MalaCards based summary : Mental Retardation, Autosomal Dominant 22, is also known as mrd22, and has symptoms including seizures An important gene associated with Mental Retardation, Autosomal Dominant 22 is ZBTB18 (Zinc Finger And BTB Domain Containing 18). Related phenotypes are intellectual disability and global developmental delay

Disease Ontology : 12 An autosomal dominant non-syndromic intellectual disability that has material basis in an autosomal dominant mutation of ZBTB18 on chromosome 1q44.

UniProtKB/Swiss-Prot : 72 Mental retardation, autosomal dominant 22: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD22 patients have limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low- set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures.

Related Diseases for Mental Retardation, Autosomal Dominant 22

Diseases in the Mental Retardation, Autosomal Dominant 7 family:

Mental Retardation, Autosomal Recessive 2 Mental Retardation, Autosomal Recessive 5
Mental Retardation, Autosomal Dominant 22 Mental Retardation, Autosomal Dominant 20
Mental Retardation, Autosomal Recessive 14 Mental Retardation, Autosomal Recessive 16
Mental Retardation, Autosomal Recessive 18 Mental Retardation, Autosomal Dominant 10
Mental Retardation, Autosomal Dominant 11 Mental Retardation, Autosomal Recessive 31
Mental Retardation, Autosomal Recessive 29 Mental Retardation, Autosomal Recessive 27
Mental Retardation, Autosomal Recessive 33 Mental Retardation, Autosomal Recessive 30
Mental Retardation, Autosomal Recessive 19 Mental Retardation, Autosomal Recessive 23
Mental Retardation, Autosomal Recessive 24 Mental Retardation, Autosomal Recessive 25
Mental Retardation, Autosomal Recessive 28 Mental Retardation, Autosomal Dominant 13
Mental Retardation, Autosomal Recessive 35 Mental Retardation, Autosomal Recessive 36
Mental Retardation, Autosomal Recessive 37 Mental Retardation, Autosomal Dominant 21
Mental Retardation, Autosomal Recessive 38 Mental Retardation, Autosomal Recessive 39
Mental Retardation, Autosomal Recessive 40 Mental Retardation, Autosomal Recessive 41
Mental Retardation, Autosomal Dominant 23 Mental Retardation, Autosomal Recessive 42
Mental Retardation, Autosomal Recessive 43 Mental Retardation, Autosomal Dominant 26
Mental Retardation, Autosomal Recessive 44 Mental Retardation, Autosomal Recessive 45
Mental Retardation, Autosomal Dominant 29 Mental Retardation, Autosomal Dominant 30
Mental Retardation, Autosomal Recessive 46 Mental Retardation, Autosomal Dominant 31
Mental Retardation, Autosomal Recessive 47 Mental Retardation, Autosomal Recessive 48
Mental Retardation, Autosomal Dominant 33 Mental Retardation, Autosomal Dominant 34
Mental Retardation, Autosomal Dominant 35 Mental Retardation, Autosomal Dominant 36
Mental Retardation, Autosomal Dominant 38 Mental Retardation, Autosomal Recessive 50
Mental Retardation, Autosomal Dominant 39 Mental Retardation, Autosomal Dominant 40
Mental Retardation, Autosomal Recessive 51 Mental Retardation, Autosomal Recessive 52
Mental Retardation, Autosomal Recessive 53 Mental Retardation, Autosomal Dominant 41
Mental Retardation, Autosomal Dominant 42 Mental Retardation, Autosomal Dominant 43
Mental Retardation, Autosomal Recessive 54 Mental Retardation, Autosomal Recessive 56
Mental Retardation, Autosomal Recessive 57 Mental Retardation, Autosomal Recessive 58
Mental Retardation, Autosomal Recessive 59 Mental Retardation, Autosomal Recessive 60
Mental Retardation, Autosomal Dominant 45 Mental Retardation, Autosomal Dominant 46
Mental Retardation, Autosomal Dominant 47 Mental Retardation, Autosomal Dominant 48
Mental Retardation, Autosomal Recessive 61 Mental Retardation, Autosomal Dominant 50
Mental Retardation, Autosomal Dominant 51 Mental Retardation, Autosomal Dominant 52
Mental Retardation, Autosomal Dominant 53 Mental Retardation, Autosomal Dominant 54
Mental Retardation, Autosomal Dominant 56 Mental Retardation, Autosomal Dominant 57
Mental Retardation, Autosomal Recessive 63 Mental Retardation, Autosomal Recessive 64
Mental Retardation, Autosomal Dominant 58 Mental Retardation, Autosomal Recessive 65
Mental Retardation, Autosomal Recessive 66 Autosomal Dominant Mental Retardation 55

Symptoms & Phenotypes for Mental Retardation, Autosomal Dominant 22

Human phenotypes related to Mental Retardation, Autosomal Dominant 22:

58 31 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
3 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
4 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
5 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
6 smooth philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000319
7 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
8 prominent forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0011220
9 micrognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000347
10 low-set ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000369
11 epicanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000286
12 round face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000311
13 thin vermilion border 58 31 hallmark (90%) Very frequent (99-80%) HP:0000233
14 aplasia/hypoplasia of the corpus callosum 58 31 hallmark (90%) Very frequent (99-80%) HP:0007370
15 seizure 31 hallmark (90%) HP:0001250
16 seizures 58 Very frequent (99-80%)
17 agenesis of corpus callosum 31 HP:0001274
18 absent speech 31 HP:0001344
19 thin upper lip vermilion 31 HP:0000219
20 generalized hypotonia 31 HP:0001290
21 abnormality of the pinna 31 HP:0000377

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
hypotonia
agenesis of the corpus callosum
mental retardation
delayed psychomotor development
more
Head And Neck Head:
microcephaly

Growth Height:
short stature

Head And Neck Mouth:
thin upper lip

Growth Other:
poor growth

Head And Neck Eyes:
hypertelorism
epicanthal folds

Head And Neck Face:
smooth philtrum
prominent forehead
micrognathia
round face

Head And Neck Ears:
low-set ears
malformed ears

Head And Neck Nose:
flat nasal bridge

Clinical features from OMIM®:

612337 (Updated 05-Apr-2021)

UMLS symptoms related to Mental Retardation, Autosomal Dominant 22:


seizures

GenomeRNAi Phenotypes related to Mental Retardation, Autosomal Dominant 22 according to GeneCards Suite gene sharing:

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.44 ZBTB18
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-121 9.44 ZBTB18
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-123 9.44 ZBTB18
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.44 ZBTB18
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.44 CHST12
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-154 9.44 ZBTB18
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-164 9.44 ZBTB18
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-172 9.44 CHST12
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 9.44 CHST12
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-2 9.44 ZBTB18
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-21 9.44 CHST12
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-215 9.44 CHST12
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-26 9.44 ZBTB18

Drugs & Therapeutics for Mental Retardation, Autosomal Dominant 22

Search Clinical Trials , NIH Clinical Center for Mental Retardation, Autosomal Dominant 22

Genetic Tests for Mental Retardation, Autosomal Dominant 22

Genetic tests related to Mental Retardation, Autosomal Dominant 22:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Dominant 22 29 ZBTB18

Anatomical Context for Mental Retardation, Autosomal Dominant 22

Publications for Mental Retardation, Autosomal Dominant 22

Articles related to Mental Retardation, Autosomal Dominant 22:

(show all 13)
# Title Authors PMID Year
1
Toward clinical and molecular understanding of pathogenic variants in the ZBTB18 gene. 57 6
29573576 2018
2
Further evidence that de novo missense and truncating variants in ZBTB18 cause intellectual disability with variable features. 57 6
27598823 2017
3
Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU. 57 6
28283832 2017
4
Identification of novel genetic causes of Rett syndrome-like phenotypes. 57 6
26740508 2016
5
A de novo non-sense mutation in ZBTB18 in a patient with features of the 1q43q44 microdeletion syndrome. 6 57
24193349 2014
6
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
7
RP58/ZNF238 directly modulates proneurogenic gene levels and is required for neuronal differentiation and brain expansion. 57
22095278 2012
8
High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44. 57
21800092 2012
9
Clinical and molecular characteristics of 1qter microdeletion syndrome: delineating a critical region for corpus callosum agenesis/hypogenesis. 57
18178631 2008
10
Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. 57
17668379 2007
11
Submicroscopic subtelomeric 1qter deletions: a recognisable phenotype? 57
11303509 2001
12
Deletion of the distal long arm of chromosome 1: a definable syndrome. 57
4073121 1985
13
Molecular cloning of a dehydration-responsive protein gene (MRD22) from mulberry, and determination of abiotic stress patterns of MRD22 gene expression. 61
25895340 2014

Variations for Mental Retardation, Autosomal Dominant 22

ClinVar genetic disease variations for Mental Retardation, Autosomal Dominant 22:

6 (show all 28)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ZBTB18 NM_006352.4(ZBTB18):c.572del (p.Asp190_Ser191insTer) Deletion Pathogenic 397517 rs1060499655 GRCh37: 1:244217675-244217675
GRCh38: 1:244054373-244054373
2 ZBTB18 NM_006352.4(ZBTB18):c.556C>T (p.Arg186Ter) SNV Pathogenic 417741 rs1064792999 GRCh37: 1:244217659-244217659
GRCh38: 1:244054357-244054357
3 ZBTB18 NM_205768.2(ZBTB18):c.142C>T (p.Arg48Ter) SNV Pathogenic 431091 rs1135401770 GRCh37: 1:244217218-244217218
GRCh38: 1:244053916-244053916
4 ZBTB18 NM_006352.4(ZBTB18):c.1363C>T (p.Arg455Cys) SNV Pathogenic 440857 rs750922282 GRCh37: 1:244218466-244218466
GRCh38: 1:244055164-244055164
5 ZBTB18 NM_205768.2(ZBTB18):c.1444C>T (p.Arg482Cys) SNV Pathogenic 548012 rs1553270634 GRCh37: 1:244218520-244218520
GRCh38: 1:244055218-244055218
6 ZBTB18 NM_006352.4(ZBTB18):c.370G>T (p.Glu124Ter) SNV Pathogenic 88856 rs398122406 GRCh37: 1:244217473-244217473
GRCh38: 1:244054171-244054171
7 ZBTB18 NM_006352.4(ZBTB18):c.940_941insG (p.Leu314fs) Insertion Pathogenic 801642 rs1572531281 GRCh37: 1:244218043-244218044
GRCh38: 1:244054741-244054742
8 ZBTB18 NM_205768.3(ZBTB18):c.1143C>A (p.Cys381Ter) SNV Pathogenic 975780 GRCh37: 1:244218219-244218219
GRCh38: 1:244054917-244054917
9 ZBTB18 NM_205768.2(ZBTB18):c.1183C>T (p.Gln395Ter) SNV Pathogenic 225892 rs875989786 GRCh37: 1:244218259-244218259
GRCh38: 1:244054957-244054957
10 ZBTB18 NM_205768.3(ZBTB18):c.753_754del (p.Ser252fs) Deletion Pathogenic 992626 GRCh37: 1:244217828-244217829
GRCh38: 1:244054526-244054527
11 ZBTB18 NM_205768.2(ZBTB18):c.1382A>G (p.Asn461Ser) SNV Pathogenic 208690 rs797044885 GRCh37: 1:244218458-244218458
GRCh38: 1:244055156-244055156
12 ZBTB18 NM_205768.3(ZBTB18):c.1391G>A SNV Pathogenic 617452 rs1558149913 GRCh37: 1:244218467-244218467
GRCh38: 1:244055165-244055165
13 ZBTB18 NM_006352.4(ZBTB18):c.916_917del (p.Arg306fs) Deletion Pathogenic 225922 rs1085307108 GRCh37: 1:244218019-244218020
GRCh38: 1:244054717-244054718
14 ZBTB18 NM_006352.4(ZBTB18):c.1256T>G (p.Phe419Cys) SNV Likely pathogenic 807724 rs1572531730 GRCh37: 1:244218359-244218359
GRCh38: 1:244055057-244055057
15 ZBTB18 NM_205768.3(ZBTB18):c.1378C>T (p.His460Tyr) SNV Likely pathogenic 1032618 GRCh37: 1:244218454-244218454
GRCh38: 1:244055152-244055152
16 ZBTB18 NM_205768.3(ZBTB18):c.244_246dup (p.Pro82dup) Duplication Likely pathogenic 988750 GRCh37: 1:244217317-244217318
GRCh38: 1:244054015-244054016
17 ZBTB18 NM_205768.3(ZBTB18):c.1391G>C (p.Arg464Pro) SNV Likely pathogenic 975781 GRCh37: 1:244218467-244218467
GRCh38: 1:244055165-244055165
18 ZBTB18 NM_205768.3(ZBTB18):c.1473C>G (p.Tyr491Ter) SNV Likely pathogenic 873440 GRCh37: 1:244218549-244218549
GRCh38: 1:244055247-244055247
19 ZBTB18 NM_006352.4(ZBTB18):c.133T>C (p.Cys45Arg) SNV Likely pathogenic 224125 rs869312689 GRCh37: 1:244217236-244217236
GRCh38: 1:244053934-244053934
20 ZBTB18 NM_006352.4(ZBTB18):c.1274T>C (p.Leu425Pro) SNV Likely pathogenic 559857 rs1553270599 GRCh37: 1:244218377-244218377
GRCh38: 1:244055075-244055075
21 ZBTB18 NM_205768.2(ZBTB18):c.1355G>A (p.Cys452Tyr) SNV Likely pathogenic 666591 rs1572531830 GRCh37: 1:244218431-244218431
GRCh38: 1:244055129-244055129
22 ZBTB18 NM_006352.4(ZBTB18):c.1438G>T (p.Asp480Tyr) SNV Likely pathogenic 689797 rs1572532005 GRCh37: 1:244218541-244218541
GRCh38: 1:244055239-244055239
23 ZBTB18 NM_006352.4(ZBTB18):c.1466A>C (p.His489Pro) SNV Likely pathogenic 545593 rs1553270640 GRCh37: 1:244218569-244218569
GRCh38: 1:244055267-244055267
24 ZBTB18 NM_205768.3(ZBTB18):c.1307G>A (p.Arg436His) SNV Uncertain significance 976114 GRCh37: 1:244218383-244218383
GRCh38: 1:244055081-244055081
25 ZBTB18 NM_205768.3(ZBTB18):c.1307G>T (p.Arg436Leu) SNV Uncertain significance 813952 rs1572531765 GRCh37: 1:244218383-244218383
GRCh38: 1:244055081-244055081
26 ZBTB18 NM_205768.3(ZBTB18):c.1054G>A (p.Glu352Lys) SNV Uncertain significance 1027957 GRCh37: 1:244218130-244218130
GRCh38: 1:244054828-244054828
27 ZBTB18 NM_205768.3(ZBTB18):c.1306C>T (p.Arg436Cys) SNV Uncertain significance 1027958 GRCh37: 1:244218382-244218382
GRCh38: 1:244055080-244055080
28 ZBTB18 NM_205768.3(ZBTB18):c.1347C>G (p.Cys449Trp) SNV Uncertain significance 1027959 GRCh37: 1:244218423-244218423
GRCh38: 1:244055121-244055121

Expression for Mental Retardation, Autosomal Dominant 22

Search GEO for disease gene expression data for Mental Retardation, Autosomal Dominant 22.

Pathways for Mental Retardation, Autosomal Dominant 22

GO Terms for Mental Retardation, Autosomal Dominant 22

Molecular functions related to Mental Retardation, Autosomal Dominant 22 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 serine-type peptidase activity GO:0008236 8.62 TPSD1 TPSB2

Sources for Mental Retardation, Autosomal Dominant 22

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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