HPMRS4
MCID: HYP580
MIFTS: 29

Hyperphosphatasia with Mental Retardation Syndrome 4 (HPMRS4)

Categories: Gastrointestinal diseases, Genetic diseases, Mental diseases, Neuronal diseases

Aliases & Classifications for Hyperphosphatasia with Mental Retardation Syndrome 4

MalaCards integrated aliases for Hyperphosphatasia with Mental Retardation Syndrome 4:

Name: Hyperphosphatasia with Mental Retardation Syndrome 4 57 72 29 6 70
Hpmrs4 57 72
Glycosylphosphatidylinositol Biosynthesis Defect 10; Gpibd10 57
Hyperphosphatasia, with Mental Retardation Syndrome, Type 4 39
Glycosylphosphatidylinositol Biosynthesis Defect 10 57
Gpibd10 57

Characteristics:

OMIM®:

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

Miscellaneous:
onset in infancy


HPO:

31
hyperphosphatasia with mental retardation syndrome 4:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



Summaries for Hyperphosphatasia with Mental Retardation Syndrome 4

OMIM® : 57 Hyperphosphatasia with mental retardation syndrome-4 is an autosomal recessive neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase (summary by Howard et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293). (615716) (Updated 05-Apr-2021)

MalaCards based summary : Hyperphosphatasia with Mental Retardation Syndrome 4, also known as hpmrs4, is related to autosomal recessive disease and hypotonia, and has symptoms including involuntary movements and myoclonic seizures. An important gene associated with Hyperphosphatasia with Mental Retardation Syndrome 4 is PGAP3 (Post-GPI Attachment To Proteins Phospholipase 3). Affiliated tissues include cerebellum, heart and brain, and related phenotypes are microcephaly and cleft palate

UniProtKB/Swiss-Prot : 72 Hyperphosphatasia with mental retardation syndrome 4: An autosomal recessive neurologic disorder characterized by profound developmental delay, severe mental retardation, no speech, psychomotor delay, postnatal microcephaly, and elevated serum alkaline phosphatase.

Related Diseases for Hyperphosphatasia with Mental Retardation Syndrome 4

Diseases in the Hyperphosphatasia with Mental Retardation Syndrome 1 family:

Hyperphosphatasia with Mental Retardation Syndrome 3 Hyperphosphatasia with Mental Retardation Syndrome 2
Hyperphosphatasia with Mental Retardation Syndrome 4 Hyperphosphatasia with Mental Retardation Syndrome 6

Diseases related to Hyperphosphatasia with Mental Retardation Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 autosomal recessive disease 10.4
2 hypotonia 10.4
3 cleft palate, isolated 10.3
4 dysphagia 10.3
5 megalocornea 10.2
6 alacrima, achalasia, and mental retardation syndrome 10.2
7 hyperphosphatasia-intellectual disability syndrome 10.2

Graphical network of the top 20 diseases related to Hyperphosphatasia with Mental Retardation Syndrome 4:



Diseases related to Hyperphosphatasia with Mental Retardation Syndrome 4

Symptoms & Phenotypes for Hyperphosphatasia with Mental Retardation Syndrome 4

Human phenotypes related to Hyperphosphatasia with Mental Retardation Syndrome 4:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 occasional (7.5%) HP:0000252
2 cleft palate 31 occasional (7.5%) HP:0000175
3 growth delay 31 occasional (7.5%) HP:0001510
4 intellectual disability 31 HP:0001249
5 global developmental delay 31 HP:0001263
6 hypertelorism 31 HP:0000316
7 wide nasal bridge 31 HP:0000431
8 upslanted palpebral fissure 31 HP:0000582
9 thin upper lip vermilion 31 HP:0000219
10 involuntary movements 31 HP:0004305
11 tented upper lip vermilion 31 HP:0010804
12 broad nasal tip 31 HP:0000455
13 generalized hypotonia 31 HP:0001290
14 inability to walk 31 HP:0002540
15 bruxism 31 HP:0003763
16 elevated alkaline phosphatase 31 HP:0003155
17 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
hypertelorism
epicanthal folds
upslanting palpebral fissures

Head And Neck Nose:
broad nasal tip
broad nasal bridge

Muscle Soft Tissue:
hypotonia

Head And Neck Teeth:
abnormal dentition

Growth Other:
poor growth (1 patient)

Cardiovascular Heart:
congenital heart defects (in 1 family)

Skin Nails Hair Hair:
thin, sparse hair (in 1 family)

Neurologic Central Nervous System:
involuntary movements
inability to walk
hypoplastic corpus callosum (in some patients)
lack of speech development
delayed psychomotor development, severe
more
Head And Neck Mouth:
bruxism
thin upper lip
cleft palate (in some patients)
tented upper lip
gum hypertrophy (in 1 patient)

Laboratory Abnormalities:
increased serum alkaline phosphatase

Head And Neck Ears:
hearing loss (in some patients)
large fleshy earlobes
ear pit

Head And Neck Head:
microcephaly (-2 to -3 sd) (in some patients)
large anterior fontanel (in 1 family)

Skeletal Feet:
pes equinovarus (in 1 patient)

Clinical features from OMIM®:

615716 (Updated 05-Apr-2021)

UMLS symptoms related to Hyperphosphatasia with Mental Retardation Syndrome 4:


involuntary movements; myoclonic seizures

Drugs & Therapeutics for Hyperphosphatasia with Mental Retardation Syndrome 4

Search Clinical Trials , NIH Clinical Center for Hyperphosphatasia with Mental Retardation Syndrome 4

Genetic Tests for Hyperphosphatasia with Mental Retardation Syndrome 4

Genetic tests related to Hyperphosphatasia with Mental Retardation Syndrome 4:

# Genetic test Affiliating Genes
1 Hyperphosphatasia with Mental Retardation Syndrome 4 29 PGAP3

Anatomical Context for Hyperphosphatasia with Mental Retardation Syndrome 4

MalaCards organs/tissues related to Hyperphosphatasia with Mental Retardation Syndrome 4:

40
Cerebellum, Heart, Brain

Publications for Hyperphosphatasia with Mental Retardation Syndrome 4

Articles related to Hyperphosphatasia with Mental Retardation Syndrome 4:

# Title Authors PMID Year
1
Delineating the phenotypic spectrum of hyperphosphatasia with mental retardation syndrome 4 in 14 patients of Middle-Eastern origin. 61 57 6
30345601 2018
2
Hyperphosphatasia with mental retardation syndrome type 4 In two siblings-expanding the phenotypic and mutational spectrum. 6 57
30217754 2019
3
Expanding the phenome and variome of skeletal dysplasia. 57 6
29620724 2018
4
Mutations in PGAP3 impair GPI-anchor maturation, causing a subtype of hyperphosphatasia with mental retardation. 6 57
24439110 2014
5
Phenotypic variability in hyperphosphatasia with seizures and neurologic deficit (Mabry syndrome). 57 6
22315194 2012
6
PGAP3-related hyperphosphatasia with mental retardation syndrome: Report of 10 new patients and a homozygous founder mutation. 6
28390064 2018
7
Rare Noncoding Mutations Extend the Mutational Spectrum in the PGAP3 Subtype of Hyperphosphatasia with Mental Retardation Syndrome. 6
27120253 2016
8
PGAP3 Associated with Hyperphosphatasia with Mental Retardation Plays a Novel Role in Brain Morphogenesis and Neuronal Wiring at Early Development. 61
32726939 2020
9
A novel PGAP3 mutation in a Croatian boy with brachytelephalangy and a thin corpus callosum. 61
29531774 2018

Variations for Hyperphosphatasia with Mental Retardation Syndrome 4

ClinVar genetic disease variations for Hyperphosphatasia with Mental Retardation Syndrome 4:

6 (show all 21)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PGAP3 NM_033419.5(PGAP3):c.275G>A (p.Gly92Asp) SNV Pathogenic 125437 rs587777251 GRCh37: 17:37842179-37842179
GRCh38: 17:39685926-39685926
2 PGAP3 NM_033419.5(PGAP3):c.914A>G (p.Asp305Gly) SNV Pathogenic 125439 rs587777252 GRCh37: 17:37829105-37829105
GRCh38: 17:39672852-39672852
3 PGAP3 NM_033419.5(PGAP3):c.314C>G (p.Pro105Arg) SNV Pathogenic 125440 rs371549948 GRCh37: 17:37840968-37840968
GRCh38: 17:39684715-39684715
4 PGAP3 NM_033419.5(PGAP3):c.439dup (p.Leu147fs) Duplication Pathogenic 224646 rs869312815 GRCh37: 17:37830925-37830926
GRCh38: 17:39674672-39674673
5 PGAP3 NM_033419.5(PGAP3):c.320C>T (p.Ser107Leu) SNV Pathogenic 224643 rs202146344 GRCh37: 17:37840962-37840962
GRCh38: 17:39684709-39684709
6 PGAP3 NM_033419.5(PGAP3):c.861G>T (p.Trp287Cys) SNV Pathogenic 224641 rs869312813 GRCh37: 17:37829342-37829342
GRCh38: 17:39673089-39673089
7 PGAP3 NM_033419.5(PGAP3):c.845A>G (p.Asp282Gly) SNV Pathogenic 224644 rs869312814 GRCh37: 17:37829358-37829358
GRCh38: 17:39673105-39673105
8 PGAP3 NM_033419.5(PGAP3):c.511T>C (p.Cys171Arg) SNV Pathogenic 224647 rs869312816 GRCh37: 17:37830292-37830292
GRCh38: 17:39674039-39674039
9 PGAP3 NM_033419.5(PGAP3):c.842T>C (p.Leu281Pro) SNV Pathogenic 224648 rs869312817 GRCh37: 17:37829361-37829361
GRCh38: 17:39673108-39673108
10 PGAP3 NM_033419.5(PGAP3):c.280del (p.Trp94fs) Deletion Pathogenic 496676 rs1555610292 GRCh37: 17:37841002-37841002
GRCh38: 17:39684749-39684749
11 PGAP3 NM_033419.5(PGAP3):c.432+1G>A SNV Pathogenic 522978 rs1555610241 GRCh37: 17:37840849-37840849
GRCh38: 17:39684596-39684596
12 PGAP3 NM_033419.5(PGAP3):c.851A>G (p.His284Arg) SNV Pathogenic 599004 rs776720232 GRCh37: 17:37829352-37829352
GRCh38: 17:39673099-39673099
13 PGAP3 NM_033419.5(PGAP3):c.75_81dup (p.Val28Ter) Duplication Pathogenic 982399 GRCh37: 17:37844186-37844187
GRCh38: 17:39687933-39687934
14 PGAP3 NM_033419.5(PGAP3):c.402dup (p.Met135fs) Duplication Pathogenic 224640 rs869312812 GRCh37: 17:37840879-37840880
GRCh38: 17:39684626-39684627
15 PGAP3 NM_033419.5(PGAP3):c.850C>T (p.His284Tyr) SNV Pathogenic/Likely pathogenic 800935 rs759541820 GRCh37: 17:37829353-37829353
GRCh38: 17:39673100-39673100
16 PGAP3 NM_033419.5(PGAP3):c.507C>A (p.Tyr169Ter) SNV Pathogenic/Likely pathogenic 522596 rs1567871748 GRCh37: 17:37830296-37830296
GRCh38: 17:39674043-39674043
17 PGAP3 NM_033419.5(PGAP3):c.558-10G>A SNV Likely pathogenic 224645 rs200598755 GRCh37: 17:37829913-37829913
GRCh38: 17:39673660-39673660
18 PGAP3 NM_033419.5(PGAP3):c.*559C>T SNV Conflicting interpretations of pathogenicity 224642 rs183208638 GRCh37: 17:37828497-37828497
GRCh38: 17:39672244-39672244
19 PGAP3 NM_033419.5(PGAP3):c.209A>T (p.Tyr70Phe) SNV Uncertain significance 547988 rs146132289 GRCh37: 17:37842245-37842245
GRCh38: 17:39685992-39685992
20 PGAP3 NM_033419.5(PGAP3):c.307C>G (p.Gln103Glu) SNV Uncertain significance 1028519 GRCh37: 17:37840975-37840975
GRCh38: 17:39684722-39684722
21 PGAP3 NM_033419.5(PGAP3):c.754C>T (p.His252Tyr) SNV Uncertain significance 1031560 GRCh37: 17:37829449-37829449
GRCh38: 17:39673196-39673196

UniProtKB/Swiss-Prot genetic disease variations for Hyperphosphatasia with Mental Retardation Syndrome 4:

72
# Symbol AA change Variation ID SNP ID
1 PGAP3 p.Gly92Asp VAR_071155 rs587777251
2 PGAP3 p.Pro105Arg VAR_071156 rs371549948
3 PGAP3 p.Asp305Gly VAR_071157 rs587777252

Expression for Hyperphosphatasia with Mental Retardation Syndrome 4

Search GEO for disease gene expression data for Hyperphosphatasia with Mental Retardation Syndrome 4.

Pathways for Hyperphosphatasia with Mental Retardation Syndrome 4

GO Terms for Hyperphosphatasia with Mental Retardation Syndrome 4

Sources for Hyperphosphatasia with Mental Retardation Syndrome 4

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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