HPMRS3
MCID: HYP553
MIFTS: 24

Hyperphosphatasia with Mental Retardation Syndrome 3 (HPMRS3)

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

Aliases & Classifications for Hyperphosphatasia with Mental Retardation Syndrome 3

MalaCards integrated aliases for Hyperphosphatasia with Mental Retardation Syndrome 3:

Name: Hyperphosphatasia with Mental Retardation Syndrome 3 57 72 29 13 6
Glycosylphosphatidylinositol Biosynthesis Defect 8 57 72
Mental Retardation, Autosomal Recessive 17 57 70
Hpmrs3 57 72
Gpibd8 57 72
Mrt17 57 72
Mrt21 57 72
Hyperphosphatasia, with Mental Retardation Syndrome, Type 3 39
Glycosylphosphatidylinositol Biosynthesis Defect 8; Gpibd8 57
Mental Retardation, Autosomal Recessive 17; Mrt17 57
Mental Retardation, Autosomal Recessive 21; Mrt21 57
Mental Retardation, Autosomal Recessive 21 57
Autosomal Recessive Mental Retardation 17 72
Autosomal Recessive Mental Retardation 21 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
most patients are severely affected


HPO:

31
hyperphosphatasia with mental retardation syndrome 3:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Hyperphosphatasia with Mental Retardation Syndrome 3

OMIM® : 57 Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase (summary by Hansen et al., 2013). However, the severity of the disorder can also vary to include milder intellectual disability (Krawitz et al., 2013). 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). (614207) (Updated 20-May-2021)

MalaCards based summary : Hyperphosphatasia with Mental Retardation Syndrome 3, is also known as glycosylphosphatidylinositol biosynthesis defect 8. An important gene associated with Hyperphosphatasia with Mental Retardation Syndrome 3 is PGAP2 (Post-GPI Attachment To Proteins 2). Related phenotypes are microcephaly and intellectual disability, mild

UniProtKB/Swiss-Prot : 72 Hyperphosphatasia with mental retardation syndrome 3: An autosomal recessive disorder usually characterized by mental retardation, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase.

Related Diseases for Hyperphosphatasia with Mental Retardation Syndrome 3

Symptoms & Phenotypes for Hyperphosphatasia with Mental Retardation Syndrome 3

Human phenotypes related to Hyperphosphatasia with Mental Retardation Syndrome 3:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 occasional (7.5%) HP:0000252
2 intellectual disability, mild 31 occasional (7.5%) HP:0001256
3 cerebral atrophy 31 occasional (7.5%) HP:0002059
4 seizure 31 occasional (7.5%) HP:0001250
5 hearing impairment 31 HP:0000365
6 global developmental delay 31 HP:0001263
7 wide nasal bridge 31 HP:0000431
8 short nose 31 HP:0003196
9 intellectual disability, severe 31 HP:0010864
10 absent speech 31 HP:0001344
11 cleft palate 31 HP:0000175
12 tented upper lip vermilion 31 HP:0010804
13 broad nasal tip 31 HP:0000455
14 generalized hypotonia 31 HP:0001290
15 hyperphosphatemia 31 HP:0002905
16 elevated alkaline phosphatase 31 HP:0003155

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Ears:
hearing impairment

Head And Neck Mouth:
cleft palate
tented upper lip

Muscle Soft Tissue:
hypotonia

Head And Neck Head:
microcephaly (in some patients)

Head And Neck Nose:
short nose
broad nasal tip
broad nasal bridge

Laboratory Abnormalities:
hyperphosphatemia
increased serum alkaline phosphatase

Neurologic Central Nervous System:
hypotonia
mental retardation, severe
intellectual disability, mild (in some patients)
seizures (in some patients)
delayed psychomotor development
more

Clinical features from OMIM®:

614207 (Updated 20-May-2021)

Drugs & Therapeutics for Hyperphosphatasia with Mental Retardation Syndrome 3

Search Clinical Trials , NIH Clinical Center for Hyperphosphatasia with Mental Retardation Syndrome 3

Genetic Tests for Hyperphosphatasia with Mental Retardation Syndrome 3

Genetic tests related to Hyperphosphatasia with Mental Retardation Syndrome 3:

# Genetic test Affiliating Genes
1 Hyperphosphatasia with Mental Retardation Syndrome 3 29 PGAP2

Anatomical Context for Hyperphosphatasia with Mental Retardation Syndrome 3

Publications for Hyperphosphatasia with Mental Retardation Syndrome 3

Articles related to Hyperphosphatasia with Mental Retardation Syndrome 3:

# Title Authors PMID Year
1
Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability. 6 57
23561846 2013
2
PGAP2 mutations, affecting the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation syndrome. 6 57
23561847 2013
3
Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity. 57 6
21629298 2011
4
Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel. 57 6
21643797 2011
5
A post glycosylphosphatidylinositol (GPI) attachment to proteins, type 2 (PGAP2) variant identified in Mabry syndrome index cases: Molecular genetics of the prototypical inherited GPI disorder. 61
31805394 2020
6
A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family. 61
27871432 2016

Variations for Hyperphosphatasia with Mental Retardation Syndrome 3

ClinVar genetic disease variations for Hyperphosphatasia with Mental Retardation Syndrome 3:

6 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PGAP2 NM_014489.4(PGAP2):c.713G>C (p.Arg238Pro) SNV Pathogenic 50503 rs774843232 GRCh37: 11:3846254-3846254
GRCh38: 11:3825024-3825024
2 PGAP2 NM_014489.4(PGAP2):c.563T>C (p.Leu188Ser) SNV Pathogenic 50504 rs879255233 GRCh37: 11:3845327-3845327
GRCh38: 11:3824097-3824097
3 PGAP2 NM_014489.4(PGAP2):c.46C>T (p.Arg16Trp) SNV Pathogenic 50505 rs773359554 GRCh37: 11:3832535-3832535
GRCh38: 11:3811305-3811305
4 PGAP2 NM_014489.4(PGAP2):c.491C>T (p.Thr164Ile) SNV Pathogenic 50506 rs587776970 GRCh37: 11:3845255-3845255
GRCh38: 11:3824025-3824025
5 PGAP2 NM_014489.4(PGAP2):c.2T>G (p.Met1Arg) SNV Pathogenic 694699 rs1590215915 GRCh37: 11:3832491-3832491
GRCh38: 11:3811261-3811261
6 PGAP2 NM_014489.4(PGAP2):c.391G>T (p.Glu131Ter) SNV Pathogenic 827783 rs1590414630 GRCh37: 11:3845155-3845155
GRCh38: 11:3823925-3823925
7 PGAP2 NM_014489.4(PGAP2):c.479A>G (p.Tyr160Cys) SNV Pathogenic 50502 rs879255232 GRCh37: 11:3845243-3845243
GRCh38: 11:3824013-3824013
8 PGAP2 NM_014489.4(PGAP2):c.881C>T (p.Thr294Met) SNV Likely pathogenic 827784 rs747658866 GRCh37: 11:3846621-3846621
GRCh38: 11:3825391-3825391
9 PGAP2 NM_014489.4(PGAP2):c.449T>C (p.Phe150Ser) SNV Likely pathogenic 802653 rs1590416370 GRCh37: 11:3845213-3845213
GRCh38: 11:3823983-3823983
10 PGAP2 NM_014489.4(PGAP2):c.391dup (p.Glu131fs) Duplication Uncertain significance 802650 rs1590414565 GRCh37: 11:3845151-3845152
GRCh38: 11:3823921-3823922
11 PGAP2 NM_014489.4(PGAP2):c.349-910C>A SNV Uncertain significance 931683 GRCh37: 11:3844203-3844203
GRCh38: 11:3822973-3822973
12 PGAP2 NM_001256235.1(PGAP2):c.-64+246A>G SNV Uncertain significance 1030428 GRCh37: 11:3819219-3819219
GRCh38: 11:3797989-3797989
13 PGAP2 NM_014489.4(PGAP2):c.392A>G (p.Glu131Gly) SNV Uncertain significance 802651 rs533117826 GRCh37: 11:3845156-3845156
GRCh38: 11:3823926-3823926
14 PGAP2 NM_014489.4(PGAP2):c.395T>G (p.Val132Gly) SNV Uncertain significance 802652 rs551147697 GRCh37: 11:3845159-3845159
GRCh38: 11:3823929-3823929

UniProtKB/Swiss-Prot genetic disease variations for Hyperphosphatasia with Mental Retardation Syndrome 3:

72
# Symbol AA change Variation ID SNP ID
1 PGAP2 p.Arg16Trp VAR_069664 rs773359554
2 PGAP2 p.Tyr99Cys VAR_069665 rs879255232
3 PGAP2 p.Leu127Ser VAR_069666 rs879255233
4 PGAP2 p.Thr160Ile VAR_069667 rs780188037
5 PGAP2 p.Arg177Pro VAR_069668 rs774843232

Expression for Hyperphosphatasia with Mental Retardation Syndrome 3

Search GEO for disease gene expression data for Hyperphosphatasia with Mental Retardation Syndrome 3.

Pathways for Hyperphosphatasia with Mental Retardation Syndrome 3

GO Terms for Hyperphosphatasia with Mental Retardation Syndrome 3

Sources for Hyperphosphatasia with Mental Retardation Syndrome 3

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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