MRXSH
MCID: MNT192
MIFTS: 37

Mental Retardation, X-Linked, Syndromic, Hedera Type (MRXSH)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mental Retardation, X-Linked, Syndromic, Hedera Type

MalaCards integrated aliases for Mental Retardation, X-Linked, Syndromic, Hedera Type:

Name: Mental Retardation, X-Linked, Syndromic, Hedera Type 57 12 29 6 39
Mental Retardation, X-Linked, with Epilepsy 72 13 70
Mrxsh 57 12 58
Mrxe 57 12 72
Syndromic X-Linked Intellectual Disability Hedera Type 12 15
Mental Retardation, X-Linked, with Epilepsy; Mrxe 57
X-Linked Intellectual Disability, Hedera Type 58

Characteristics:

Orphanet epidemiological data:

58
x-linked intellectual disability, hedera type
Inheritance: X-linked recessive; Age of onset: Infancy;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
neurodegeneration
variable expressivity
onset in infancy
progressive disorder
three unrelated families have been reported (last curated april 2020)

Inheritance:
x-linked recessive


HPO:

31
mental retardation, x-linked, syndromic, hedera type:
Onset and clinical course variable expressivity infantile onset
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Mental Retardation, X-Linked, Syndromic, Hedera Type

OMIM® : 57 The Hedera type of X-linked syndromic mental retardation (MRXSH) is characterized by global developmental delay apparent from infancy and progressive neurologic decline with abnormal movements, spasticity, and seizures. Brain imaging shows volume loss of cortical white and gray matter, thin corpus callosum, and myelination defects, consistent with a neurodegenerative process. Only males are affected (summary by Hirose et al., 2019). (300423) (Updated 05-Apr-2021)

MalaCards based summary : Mental Retardation, X-Linked, Syndromic, Hedera Type, also known as mental retardation, x-linked, with epilepsy, is related to generalized epilepsy with febrile seizures plus and neonatal period electroclinical syndrome, and has symptoms including drop attack An important gene associated with Mental Retardation, X-Linked, Syndromic, Hedera Type is ATP6AP2 (ATPase H+ Transporting Accessory Protein 2), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Phagosome. Related phenotypes are intellectual disability and bilateral tonic-clonic seizure

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by mild to moderate mental retardation and epilepsy that has material basis in mutation in the ATP6AP2 gene on chromosome Xp11.

UniProtKB/Swiss-Prot : 72 Mental retardation, X-linked, with epilepsy: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXE patients manifest mild to moderate mental retardation associated with epilepsy, delays in motor milestones and speech acquisition in infancy.

Related Diseases for Mental Retardation, X-Linked, Syndromic, Hedera Type

Diseases related to Mental Retardation, X-Linked, Syndromic, Hedera Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 generalized epilepsy with febrile seizures plus 9.8 LGI1 ARX
2 neonatal period electroclinical syndrome 9.8 MT-ATP6 ARX
3 dravet syndrome 9.6 LGI1 ARX
4 episodic ataxia 9.6 MT-ATP6 LGI1
5 optic nerve disease 9.5 MT-ATP6 LGI1
6 early myoclonic encephalopathy 9.5 MT-ATP6 LGI1 ARX
7 epilepsy 9.2 MT-ATP6 LGI1 ATP6AP2 ARX

Graphical network of the top 20 diseases related to Mental Retardation, X-Linked, Syndromic, Hedera Type:



Diseases related to Mental Retardation, X-Linked, Syndromic, Hedera Type

Symptoms & Phenotypes for Mental Retardation, X-Linked, Syndromic, Hedera Type

Human phenotypes related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

58 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 bilateral tonic-clonic seizure 31 hallmark (90%) HP:0002069
3 delayed speech and language development 58 31 frequent (33%) Frequent (79-30%) HP:0000750
4 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
5 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
6 extrapyramidal muscular rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0007076
7 atonic seizure 58 31 frequent (33%) Frequent (79-30%) HP:0010819
8 hyporeflexia of lower limbs 58 31 frequent (33%) Frequent (79-30%) HP:0002600
9 hyporeflexia of upper limbs 58 31 frequent (33%) Frequent (79-30%) HP:0012391
10 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
11 pes planus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001763
12 slurred speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0001350
13 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
14 left ventricular hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001712
15 dysmetria 58 31 occasional (7.5%) Occasional (29-5%) HP:0001310
16 weak voice 58 31 occasional (7.5%) Occasional (29-5%) HP:0001621
17 babinski sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0003487
18 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
19 cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001272
20 frequent falls 58 31 occasional (7.5%) Occasional (29-5%) HP:0002359
21 echolalia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010529
22 inability to walk 58 31 occasional (7.5%) Occasional (29-5%) HP:0002540
23 drooling 58 31 occasional (7.5%) Occasional (29-5%) HP:0002307
24 apraxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002186
25 absent achilles reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0003438
26 hypomimic face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000338
27 action tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002345
28 calcaneovalgus deformity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001848
29 astereognosia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010527
30 agraphesthesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011812
31 gait disturbance 58 31 Occasional (29-5%) HP:0001288
32 hyporeflexia 31 HP:0001265
33 generalized tonic-clonic seizures 58 Very frequent (99-80%)
34 cerebral atrophy 31 HP:0002059
35 parkinsonism 31 HP:0001300
36 bradykinesia 31 HP:0002067

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
cerebellar atrophy
cerebral atrophy
abnormal myelination
delayed motor development
more
Neurologic Peripheral Nervous System:
hyporeflexia (family a)

Clinical features from OMIM®:

300423 (Updated 05-Apr-2021)

UMLS symptoms related to Mental Retardation, X-Linked, Syndromic, Hedera Type:


drop attack

Drugs & Therapeutics for Mental Retardation, X-Linked, Syndromic, Hedera Type

Search Clinical Trials , NIH Clinical Center for Mental Retardation, X-Linked, Syndromic, Hedera Type

Genetic Tests for Mental Retardation, X-Linked, Syndromic, Hedera Type

Genetic tests related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

# Genetic test Affiliating Genes
1 Mental Retardation, X-Linked, Syndromic, Hedera Type 29 ATP6AP2

Anatomical Context for Mental Retardation, X-Linked, Syndromic, Hedera Type

Publications for Mental Retardation, X-Linked, Syndromic, Hedera Type

Articles related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

# Title Authors PMID Year
1
ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration. 57 6
30985297 2019
2
A splice site mutation in ATP6AP2 causes X-linked intellectual disability, epilepsy, and parkinsonism. 6 57
26467484 2015
3
A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor. 57 6
15746149 2005
4
Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4. 6 57
11782983 2002
5
Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). 61
23595882 2013
6
The role of individual domains and the significance of shedding of ATP6AP2/(pro)renin receptor in vacuolar H(+)-ATPase biogenesis. 61
24223829 2013

Variations for Mental Retardation, X-Linked, Syndromic, Hedera Type

ClinVar genetic disease variations for Mental Retardation, X-Linked, Syndromic, Hedera Type:

6 (show all 32)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ATP6AP2 NM_005765.3(ATP6AP2):c.321C>T (p.Asp107=) SNV Pathogenic 10801 rs121918521 GRCh37: X:40456521-40456521
GRCh38: X:40597269-40597269
2 ATP6AP2 NM_005765.3(ATP6AP2):c.168+6T>A SNV Pathogenic 375269 rs1057519331 GRCh37: X:40448374-40448374
GRCh38: X:40589122-40589122
3 ATP6AP2 NM_005765.3(ATP6AP2):c.301-11_301-10del Deletion Pathogenic 869368 GRCh37: X:40456490-40456491
GRCh38: X:40597238-40597239
4 ATP6AP2 NM_005765.3(ATP6AP2):c.596G>A (p.Arg199His) SNV Uncertain significance 204918 rs751433380 GRCh37: X:40458851-40458851
GRCh38: X:40599599-40599599
5 ATP6AP2 NM_005765.3(ATP6AP2):c.408G>A (p.Met136Ile) SNV Uncertain significance 465129 rs1555977799 GRCh37: X:40456790-40456790
GRCh38: X:40597538-40597538
6 ATP6AP2 NM_005765.3(ATP6AP2):c.840C>G (p.Ile280Met) SNV Uncertain significance 465131 rs1555978066 GRCh37: X:40460115-40460115
GRCh38: X:40600863-40600863
7 ATP6AP2 NM_005765.3(ATP6AP2):c.953C>A (p.Ala318Asp) SNV Uncertain significance 465132 rs1555978614 GRCh37: X:40464907-40464907
GRCh38: X:40605655-40605655
8 ATP6AP2 NC_000023.11:g.(?_40581046)_(40605775_?)dup Duplication Uncertain significance 832810 GRCh37: X:40440298-40465027
GRCh38:
9 ATP6AP2 NM_005765.3(ATP6AP2):c.1015A>G (p.Ile339Val) SNV Uncertain significance 854936 GRCh37: X:40464969-40464969
GRCh38: X:40605717-40605717
10 ATP6AP2 NM_005765.3(ATP6AP2):c.50A>G (p.Asn17Ser) SNV Uncertain significance 862603 GRCh37: X:40448250-40448250
GRCh38: X:40588998-40588998
11 ATP6AP2 NM_005765.3(ATP6AP2):c.428T>C (p.Val143Ala) SNV Uncertain significance 970898 GRCh37: X:40456810-40456810
GRCh38: X:40597558-40597558
12 ATP6AP2 NM_005765.3(ATP6AP2):c.858G>A (p.Ala286=) SNV Uncertain significance 533691 rs1555978069 GRCh37: X:40460133-40460133
GRCh38: X:40600881-40600881
13 ATP6AP2 NM_005765.3(ATP6AP2):c.463C>T (p.Arg155Cys) SNV Uncertain significance 204911 rs146371390 GRCh37: X:40456845-40456845
GRCh38: X:40597593-40597593
14 overlap with 11 genes NC_000023.10:g.(?_39911342)_(41782261_?)dup Duplication Uncertain significance 533692 GRCh37: X:39911342-41782261
GRCh38:
15 ATP6AP2 NM_005765.3(ATP6AP2):c.315T>G (p.Ser105Arg) SNV Uncertain significance 204917 rs745748841 GRCh37: X:40456515-40456515
GRCh38: X:40597263-40597263
16 ATP6AP2 NM_005765.3(ATP6AP2):c.469C>T (p.Arg157Cys) SNV Uncertain significance 955848 GRCh37: X:40456851-40456851
GRCh38: X:40597599-40597599
17 ATP6AP2 NM_005765.3(ATP6AP2):c.33G>A (p.Val11=) SNV Uncertain significance 1010312 GRCh37: X:40440350-40440350
GRCh38: X:40581098-40581098
18 ATP6AP2 NM_005765.3(ATP6AP2):c.922A>C (p.Asn308His) SNV Uncertain significance 380358 rs756836341 GRCh37: X:40464876-40464876
GRCh38: X:40605624-40605624
19 ATP6AP2 NM_005765.3(ATP6AP2):c.160G>T (p.Val54Leu) SNV Uncertain significance 852040 GRCh37: X:40448360-40448360
GRCh38: X:40589108-40589108
20 ATP6AP2 NM_005765.3(ATP6AP2):c.530A>G (p.Asn177Ser) SNV Uncertain significance 1016932 GRCh37: X:40456912-40456912
GRCh38: X:40597660-40597660
21 ATP6AP2 NM_005765.3(ATP6AP2):c.289C>T (p.Pro97Ser) SNV Uncertain significance 1023367 GRCh37: X:40450606-40450606
GRCh38: X:40591354-40591354
22 ATP6AP2 NM_005765.3(ATP6AP2):c.490G>A (p.Val164Ile) SNV Uncertain significance 204912 rs142013283 GRCh37: X:40456872-40456872
GRCh38: X:40597620-40597620
23 ATP6AP2 NM_005765.3(ATP6AP2):c.490G>A (p.Val164Ile) SNV Uncertain significance 204912 rs142013283 GRCh37: X:40456872-40456872
GRCh38: X:40597620-40597620
24 ATP6AP2 NM_005765.3(ATP6AP2):c.218G>A (p.Arg73Gln) SNV Uncertain significance 861472 GRCh37: X:40450535-40450535
GRCh38: X:40591283-40591283
25 ATP6AP2 NM_005765.3(ATP6AP2):c.455G>A (p.Arg152His) SNV Uncertain significance 1040448 GRCh37: X:40456837-40456837
GRCh38: X:40597585-40597585
26 ATP6AP2 NM_005765.3(ATP6AP2):c.516T>C (p.Ser172=) SNV Likely benign 759346 rs775818303 GRCh37: X:40456898-40456898
GRCh38: X:40597646-40597646
27 ATP6AP2 NM_005765.3(ATP6AP2):c.1050T>C (p.Asp350=) SNV Benign 199113 rs79790275 GRCh37: X:40465004-40465004
GRCh38: X:40605752-40605752
28 ATP6AP2 NM_005765.3(ATP6AP2):c.285G>A (p.Ser95=) SNV Benign 128486 rs34217273 GRCh37: X:40450602-40450602
GRCh38: X:40591350-40591350
29 ATP6AP2 NM_005765.3(ATP6AP2):c.868G>C (p.Ala290Pro) SNV Benign 128487 rs35798522 GRCh37: X:40464822-40464822
GRCh38: X:40605570-40605570
30 ATP6AP2 NM_005765.3(ATP6AP2):c.38-5T>C SNV Benign 136465 rs190477001 GRCh37: X:40448233-40448233
GRCh38: X:40588981-40588981
31 ATP6AP2 NM_005765.3(ATP6AP2):c.189C>T (p.Leu63=) SNV Benign 136463 rs150392503 GRCh37: X:40450506-40450506
GRCh38: X:40591254-40591254
32 ATP6AP2 NM_005765.3(ATP6AP2):c.268C>G (p.Pro90Ala) SNV Benign 95311 rs9014 GRCh37: X:40450585-40450585
GRCh38: X:40591333-40591333

Expression for Mental Retardation, X-Linked, Syndromic, Hedera Type

Search GEO for disease gene expression data for Mental Retardation, X-Linked, Syndromic, Hedera Type.

Pathways for Mental Retardation, X-Linked, Syndromic, Hedera Type

GO Terms for Mental Retardation, X-Linked, Syndromic, Hedera Type

Cellular components related to Mental Retardation, X-Linked, Syndromic, Hedera Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ficolin-1-rich granule membrane GO:0101003 8.96 TCIRG1 ATP6AP2
2 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.62 TCIRG1 ATP6AP2

Biological processes related to Mental Retardation, X-Linked, Syndromic, Hedera Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.5 TCIRG1 MT-ATP6 ATP6V1E2
2 proton transmembrane transport GO:1902600 9.26 TCIRG1 ATP6V1E2
3 insulin receptor signaling pathway GO:0008286 9.16 TCIRG1 ATP6V1E2
4 transferrin transport GO:0033572 8.96 TCIRG1 ATP6V1E2
5 phagosome acidification GO:0090383 8.62 TCIRG1 ATP6V1E2

Molecular functions related to Mental Retardation, X-Linked, Syndromic, Hedera Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proton transmembrane transporter activity GO:0015078 8.96 TCIRG1 MT-ATP6
2 proton-transporting ATPase activity, rotational mechanism GO:0046961 8.62 TCIRG1 ATP6V1E2

Sources for Mental Retardation, X-Linked, Syndromic, Hedera Type

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
Content
Loading form....