MRX98
MCID: MNT198
MIFTS: 30

Mental Retardation, X-Linked 98 (MRX98)

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

Aliases & Classifications for Mental Retardation, X-Linked 98

MalaCards integrated aliases for Mental Retardation, X-Linked 98:

Name: Mental Retardation, X-Linked 98 57 72 29 6 70
Mrx98 57 12 72
Non-Syndromic X-Linked Intellectual Disability 98 12
X-Linked Intellectual Disability, Cantagrel Type 58
Mental Retardation, X-Linked, Type 98 39
X-Linked Mental Retardation 98 12

Characteristics:

Orphanet epidemiological data:

58
x-linked intellectual disability, cantagrel type
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
incomplete penetrance
variable phenotype
onset at birth
males are more severely affected than females
onset of seizures in first months or years of life
some carrier females are unaffected
de novo mutation (in affected females)

Inheritance:
x-linked dominant


HPO:

31
mental retardation, x-linked 98:
Onset and clinical course incomplete penetrance congenital onset
Inheritance x-linked dominant inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Mental Retardation, X-Linked 98

UniProtKB/Swiss-Prot : 72 Mental retardation, X-linked 98: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRX98 patients show delayed psychomotor development, absent or poor speech development, and postnatal growth retardation, often with microcephaly. Some patients show autistic behavioral features, such as stereotypic hand movements and repetitive behaviors. Additional, more variable features include spasticity, axial hypotonia, seizures, drooling, gastroesophageal reflux, and lack of sphincter control.

MalaCards based summary : Mental Retardation, X-Linked 98, is also known as mrx98, and has symptoms including seizures and muscle spasticity. An important gene associated with Mental Retardation, X-Linked 98 is NEXMIF (Neurite Extension And Migration Factor). Affiliated tissues include eye and brain, and related phenotypes are intellectual disability and short nose

Disease Ontology : 12 A non-syndromic X-linked intellectual disability characterized by delayed psychomotor development, poor speech, behavioral abnormalities, poor overall growth, dysmorphic facial features, and often early-onset seizures, with males generally more severely affected than females that has material basis in heterozygous or hemizygous mutation in NEXMIF on chromosome Xq13.3.

OMIM® : 57 X-linked mental retardation-98 is a neurodevelopmental disorder characterized by delayed psychomotor development, poor speech, behavioral abnormalities, poor overall growth, dysmorphic facial features, and often early-onset seizures. Some carrier females are unaffected, whereas other females with mutations are affected; males tend to be more severely affected than females. It is believed that the phenotypic variability and disease manifestations in female carriers results from skewed X-inactivation or cellular mosaicism (summary by de Lange et al., 2016). (300912) (Updated 05-Apr-2021)

Symptoms & Phenotypes for Mental Retardation, X-Linked 98

Human phenotypes related to Mental Retardation, X-Linked 98:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 short nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0003196
3 neonatal hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001319
4 stereotypy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000733
5 absent speech 58 31 hallmark (90%) Very frequent (99-80%) HP:0001344
6 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
7 short philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000322
8 severe global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011344
9 tented upper lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0010804
10 autistic behavior 58 31 hallmark (90%) Very frequent (99-80%) HP:0000729
11 tetraparesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002273
12 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
13 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
14 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
15 shawl scrotum 58 31 frequent (33%) Frequent (79-30%) HP:0000049
16 esotropia 58 31 frequent (33%) Frequent (79-30%) HP:0000565
17 seizure 31 frequent (33%) HP:0001250
18 hypsarrhythmia 31 occasional (7.5%) HP:0002521
19 seizures 58 Frequent (79-30%)
20 spasticity 31 HP:0001257
21 failure to thrive 31 HP:0001508
22 ataxia 31 HP:0001251
23 global developmental delay 31 HP:0001263
24 macrotia 31 HP:0000400
25 anteverted nares 31 HP:0000463
26 growth delay 31 HP:0001510
27 open mouth 31 HP:0000194
28 prominent nasal bridge 31 HP:0000426
29 round face 31 HP:0000311
30 underdeveloped nasal alae 31 HP:0000430
31 poor eye contact 31 HP:0000817
32 feeding difficulties 31 HP:0011968
33 status epilepticus 31 HP:0002133
34 postnatal microcephaly 31 HP:0005484
35 abnormality of the musculature 58 Frequent (79-30%)
36 hyperactivity 31 HP:0000752
37 muscular hypotonia of the trunk 31 HP:0008936
38 urinary incontinence 31 HP:0000020
39 narrow forehead 31 HP:0000341
40 generalized myoclonic seizure 31 HP:0002123
41 generalized non-motor (absence) seizure 31 HP:0002121

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
ataxia
status epilepticus
myoclonic seizures
absence seizures
more
Head And Neck Nose:
short nose
prominent nasal bridge
anteverted nostrils
hypoplastic nasal alae

Head And Neck Eyes:
strabismus
poor eye contact
esotropia
downslanting eyebrows

Head And Neck Face:
short philtrum
round face
bitemporal narrowing
hypotonic face

Genitourinary Bladder:
urinary incontinence
no sphincter control

Head And Neck Ears:
large ears

Growth Other:
failure to thrive
poor growth

Abdomen Gastrointestinal:
gastroesophageal reflux
feeding difficulties
no sphincter control

Head And Neck Mouth:
open mouth

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity
autistic features
repetitive movements
stereotypical hand movements

Head And Neck Head:
microcephaly, postnatal

Muscle Soft Tissue:
axial hypotonia

Clinical features from OMIM®:

300912 (Updated 05-Apr-2021)

UMLS symptoms related to Mental Retardation, X-Linked 98:


seizures; muscle spasticity

Drugs & Therapeutics for Mental Retardation, X-Linked 98

Search Clinical Trials , NIH Clinical Center for Mental Retardation, X-Linked 98

Genetic Tests for Mental Retardation, X-Linked 98

Genetic tests related to Mental Retardation, X-Linked 98:

# Genetic test Affiliating Genes
1 Mental Retardation, X-Linked 98 29 NEXMIF

Anatomical Context for Mental Retardation, X-Linked 98

MalaCards organs/tissues related to Mental Retardation, X-Linked 98:

40
Eye, Brain

Publications for Mental Retardation, X-Linked 98

Articles related to Mental Retardation, X-Linked 98:

# Title Authors PMID Year
1
De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. 6 57
27358180 2016
2
KIAA2022 nonsense mutation in a symptomatic female. 57 6
26576034 2016
3
Delineation of the KIAA2022 mutation phenotype: two patients with X-linked intellectual disability and distinctive features. 6 57
25900396 2015
4
Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth. 6 57
23615299 2013
5
Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males. 6 57
15466006 2004
6
De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females. 57
27568816 2017
7
X-linked intellectual disability related genes disrupted by balanced X-autosome translocations. 61
26290131 2015

Variations for Mental Retardation, X-Linked 98

ClinVar genetic disease variations for Mental Retardation, X-Linked 98:

6 (show top 50) (show all 88)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NEXMIF NEXMIF, 70-KB DUP Duplication Pathogenic 88754 GRCh37:
GRCh38:
2 NEXMIF NM_001008537.3(NEXMIF):c.183del (p.Arg62fs) Deletion Pathogenic 88755 rs397518479 GRCh37: X:73964209-73964209
GRCh38: X:74744374-74744374
3 NEXMIF NM_001008537.3(NEXMIF):c.1376_1377del (p.Asp458_Cys459insTer) Deletion Pathogenic 374404 rs1057518730 GRCh37: X:73963015-73963016
GRCh38: X:74743180-74743181
4 NEXMIF NM_001008537.3(NEXMIF):c.3470C>A (p.Ser1157Ter) SNV Pathogenic 397512 rs1060499652 GRCh37: X:73960922-73960922
GRCh38: X:74741087-74741087
5 NEXMIF NM_001008537.3(NEXMIF):c.964C>T (p.Arg322Ter) SNV Pathogenic 438478 rs1556016731 GRCh37: X:73963428-73963428
GRCh38: X:74743593-74743593
6 NEXMIF NM_001008537.3(NEXMIF):c.2042del (p.Gly681fs) Deletion Pathogenic 438479 rs1556016555 GRCh37: X:73962350-73962350
GRCh38: X:74742515-74742515
7 NEXMIF NM_001008537.3(NEXMIF):c.438C>A (p.Cys146Ter) SNV Pathogenic 438477 rs1556016802 GRCh37: X:73963954-73963954
GRCh38: X:74744119-74744119
8 NEXMIF NM_001008537.3(NEXMIF):c.3011_3014del (p.Ser1004fs) Deletion Pathogenic 474068 rs1556016381 GRCh37: X:73961378-73961381
GRCh38: X:74741543-74741546
9 NEXMIF NM_001008537.3(NEXMIF):c.2673del (p.Asn891fs) Deletion Pathogenic 474064 rs1556016438 GRCh37: X:73961719-73961719
GRCh38: X:74741884-74741884
10 NEXMIF t(X;3)(q13.3;q11.2)dn Translocation Pathogenic 592173 GRCh37:
GRCh38: X:74812980-74812991
11 NEXMIF NM_001008537.3(NEXMIF):c.1456del (p.Val486fs) Deletion Pathogenic 917878 GRCh37: X:73962936-73962936
GRCh38: X:74743101-74743101
12 NEXMIF NM_001008537.3(NEXMIF):c.507_511del (p.Asp169fs) Deletion Pathogenic 639644 rs1602212778 GRCh37: X:73963881-73963885
GRCh38: X:74744046-74744050
13 NEXMIF NM_001008537.3(NEXMIF):c.3689del (p.Ala1230fs) Deletion Pathogenic 804032 rs1602210960 GRCh37: X:73960703-73960703
GRCh38: X:74740868-74740868
14 NEXMIF NM_001008537.3(NEXMIF):c.3595_3611del (p.Lys1199fs) Deletion Pathogenic 474070 rs1556016292 GRCh37: X:73960781-73960797
GRCh38: X:74740946-74740962
15 NEXMIF NM_001008537.3(NEXMIF):c.3226del (p.Thr1076fs) Deletion Pathogenic 541124 rs1556016352 GRCh37: X:73961166-73961166
GRCh38: X:74741331-74741331
16 NEXMIF NM_001008537.3(NEXMIF):c.3230del (p.Pro1077fs) Deletion Pathogenic 541125 rs1556016350 GRCh37: X:73961162-73961162
GRCh38: X:74741327-74741327
17 NEXMIF NM_001008537.3(NEXMIF):c.3800del (p.Pro1267fs) Deletion Pathogenic 574310 rs1569334937 GRCh37: X:73960592-73960592
GRCh38: X:74740757-74740757
18 NEXMIF NM_001008537.3(NEXMIF):c.2251del (p.Glu751fs) Deletion Pathogenic 578993 rs1569335485 GRCh37: X:73962141-73962141
GRCh38: X:74742306-74742306
19 NEXMIF NM_001008537.3(NEXMIF):c.3334del (p.Ile1112fs) Deletion Pathogenic 581020 rs1569335135 GRCh37: X:73961058-73961058
GRCh38: X:74741223-74741223
20 NEXMIF NM_001008537.3(NEXMIF):c.3597dup (p.Ser1200fs) Duplication Pathogenic 88753 rs397518478 GRCh37: X:73960794-73960795
GRCh38: X:74740959-74740960
21 NEXMIF NM_001008537.3(NEXMIF):c.2995_2996CT[2] (p.Ser1000fs) Microsatellite Pathogenic 224106 rs875989829 GRCh37: X:73961392-73961393
GRCh38: X:74741557-74741558
22 NEXMIF NM_001008537.3(NEXMIF):c.4248dup (p.Gly1417fs) Duplication Pathogenic 374403 rs1057518728 GRCh37: X:73960143-73960144
GRCh38: X:74740308-74740309
23 NEXMIF NM_001008537.3(NEXMIF):c.2166_2168delinsAC (p.Phe722fs) Indel Pathogenic 474060 rs1556016529 GRCh37: X:73962224-73962226
GRCh38: X:74742389-74742391
24 NEXMIF NM_001008537.3(NEXMIF):c.4075dup (p.Ser1359fs) Duplication Pathogenic 496670 rs1556016224 GRCh37: X:73960316-73960317
GRCh38: X:74740481-74740482
25 NEXMIF NM_001008537.3(NEXMIF):c.2886_2887CT[1] (p.Ser963fs) Microsatellite Pathogenic 561042 rs1569335265 GRCh37: X:73961503-73961504
GRCh38: X:74741668-74741669
26 NEXMIF NM_001008537.3(NEXMIF):c.280dup (p.Ala94fs) Duplication Pathogenic 620056 rs1569336024 GRCh37: X:73964111-73964112
GRCh38: X:74744276-74744277
27 NEXMIF NM_001008537.3(NEXMIF):c.2772_2773insTTTC (p.Glu925fs) Insertion Pathogenic 211263 rs797045646 GRCh37: X:73961619-73961620
GRCh38: X:74741784-74741785
28 NEXMIF NM_001008537.3(NEXMIF):c.1597del (p.Arg533fs) Deletion Pathogenic 435602 rs1556016632 GRCh37: X:73962795-73962795
GRCh38: X:74742960-74742960
29 NEXMIF NM_001008537.3(NEXMIF):c.1582del (p.Arg528fs) Deletion Pathogenic 167215 rs727503977 GRCh37: X:73962810-73962810
GRCh38: X:74742975-74742975
30 NEXMIF NM_001008537.3(NEXMIF):c.336G>A (p.Trp112Ter) SNV Pathogenic 983435 GRCh37: X:73964056-73964056
GRCh38: X:74744221-74744221
31 NEXMIF NM_001008537.3(NEXMIF):c.2683del (p.Ser895fs) Deletion Pathogenic 976706 GRCh37: X:73961709-73961709
GRCh38: X:74741874-74741874
32 NEXMIF NM_001008537.3(NEXMIF):c.1042C>T (p.Arg348Ter) SNV Pathogenic 280835 rs886041971 GRCh37: X:73963350-73963350
GRCh38: X:74743515-74743515
33 NEXMIF NM_001008537.3(NEXMIF):c.1882C>T (p.Arg628Ter) SNV Pathogenic 190220 rs786205208 GRCh37: X:73962510-73962510
GRCh38: X:74742675-74742675
34 NEXMIF NM_001008537.3(NEXMIF):c.1441C>T (p.Arg481Ter) SNV Pathogenic 280509 rs886041701 GRCh37: X:73962951-73962951
GRCh38: X:74743116-74743116
35 NEXMIF NM_001008537.3(NEXMIF):c.937C>T (p.Arg313Ter) SNV Pathogenic 242327 rs878854425 GRCh37: X:73963455-73963455
GRCh38: X:74743620-74743620
36 NEXMIF NM_001008537.3(NEXMIF):c.1752_1761del (p.Leu584fs) Deletion Pathogenic 1012179 GRCh37: X:73962631-73962640
GRCh38: X:74742796-74742805
37 NEXMIF NM_001008537.3(NEXMIF):c.1159G>T (p.Glu387Ter) SNV Pathogenic 1033187 GRCh37: X:73963233-73963233
GRCh38: X:74743398-74743398
38 NEXMIF NM_001008537.3(NEXMIF):c.862G>T (p.Glu288Ter) SNV Pathogenic 1033191 GRCh37: X:73963530-73963530
GRCh38: X:74743695-74743695
39 NEXMIF NM_001008537.3(NEXMIF):c.3437C>A (p.Ser1146Tyr) SNV Likely pathogenic 1030946 GRCh37: X:73960955-73960955
GRCh38: X:74741120-74741120
40 NEXMIF NM_001008537.3(NEXMIF):c.791_792del (p.Phe264fs) Deletion Likely pathogenic 974858 GRCh37: X:73963600-73963601
GRCh38: X:74743765-74743766
41 NEXMIF NM_001008537.3(NEXMIF):c.1123del (p.Glu375fs) Deletion Likely pathogenic 280599 rs886041774 GRCh37: X:73963269-73963269
GRCh38: X:74743434-74743434
42 NEXMIF NM_001008537.3(NEXMIF):c.2091_2113del (p.Asp698fs) Deletion Likely pathogenic 918142 GRCh37: X:73962279-73962301
GRCh38: X:74742444-74742466
43 NEXMIF NM_001008537.3(NEXMIF):c.4048G>A (p.Asp1350Asn) SNV Uncertain significance 625966 rs200982385 GRCh37: X:73960344-73960344
GRCh38: X:74740509-74740509
44 NEXMIF NM_001008537.3(NEXMIF):c.2147T>G (p.Val716Gly) SNV Uncertain significance 541121 rs1022775047 GRCh37: X:73962245-73962245
GRCh38: X:74742410-74742410
45 NEXMIF NM_001008537.3(NEXMIF):c.1154G>A (p.Gly385Asp) SNV Uncertain significance 541123 rs375109305 GRCh37: X:73963238-73963238
GRCh38: X:74743403-74743403
46 NEXMIF NM_001008537.3(NEXMIF):c.911G>T (p.Gly304Val) SNV Uncertain significance 574203 rs376455886 GRCh37: X:73963481-73963481
GRCh38: X:74743646-74743646
47 NEXMIF NM_001008537.3(NEXMIF):c.1904G>C (p.Arg635Thr) SNV Uncertain significance 474057 rs766086192 GRCh37: X:73962488-73962488
GRCh38: X:74742653-74742653
48 NEXMIF NM_001008537.3(NEXMIF):c.2954T>C (p.Met985Thr) SNV Uncertain significance 1030945 GRCh37: X:73961438-73961438
GRCh38: X:74741603-74741603
49 NEXMIF NM_001008537.3(NEXMIF):c.3823A>G (p.Ser1275Gly) SNV Uncertain significance 474073 rs201434271 GRCh37: X:73960569-73960569
GRCh38: X:74740734-74740734
50 NEXMIF NM_001008537.3(NEXMIF):c.3375G>A (p.Met1125Ile) SNV Uncertain significance 541126 rs1556016332 GRCh37: X:73961017-73961017
GRCh38: X:74741182-74741182

Expression for Mental Retardation, X-Linked 98

Search GEO for disease gene expression data for Mental Retardation, X-Linked 98.

Pathways for Mental Retardation, X-Linked 98

GO Terms for Mental Retardation, X-Linked 98

Sources for Mental Retardation, X-Linked 98

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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