HPMRS2
MCID: HYP442
MIFTS: 28

Hyperphosphatasia with Mental Retardation Syndrome 2 (HPMRS2)

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

Aliases & Classifications for Hyperphosphatasia with Mental Retardation Syndrome 2

MalaCards integrated aliases for Hyperphosphatasia with Mental Retardation Syndrome 2:

Name: Hyperphosphatasia with Mental Retardation Syndrome 2 57 72 29 13 6 70
Glycosylphosphatidylinositol Biosynthesis Defect 6 57 72
Hpmrs2 57 72
Gpibd6 57 72
Hyperphosphatasia, with Mental Retardation Syndrome, Type 2 39
Glycosylphosphatidylinositol Biosynthesis Defect 6; Gpibd6 57

Characteristics:

OMIM®:

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

Miscellaneous:
onset at birth


HPO:

31
hyperphosphatasia with mental retardation syndrome 2:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Hyperphosphatasia with Mental Retardation Syndrome 2

OMIM® : 57 Hyperphosphatasia with mental retardation syndrome-2 is an autosomal recessive disorder characterized by moderately to severely delayed psychomotor development, facial dysmorphism, brachytelephalangy, and increased serum alkaline phosphatase (hyperphosphatasia). Some patients may have additional features, such as cardiac septal defects or seizures (summary by Krawitz et al., 2012). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of hyperphosphatasia with mental retardation syndrome, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293). (614749) (Updated 05-Apr-2021)

MalaCards based summary : Hyperphosphatasia with Mental Retardation Syndrome 2, is also known as glycosylphosphatidylinositol biosynthesis defect 6. An important gene associated with Hyperphosphatasia with Mental Retardation Syndrome 2 is PIGO (Phosphatidylinositol Glycan Anchor Biosynthesis Class O). Affiliated tissues include heart, and related phenotypes are microcephaly and atrial septal defect

UniProtKB/Swiss-Prot : 72 Hyperphosphatasia with mental retardation syndrome 2: An autosomal recessive form of intellectual disability characterized by facial dysmorphism, brachytelephalangy, and persistent elevated serum alkaline phosphatase (hyperphosphatasia). Some patients may have additional features, such as cardiac septal defects or seizures.

Related Diseases for Hyperphosphatasia with Mental Retardation Syndrome 2

Symptoms & Phenotypes for Hyperphosphatasia with Mental Retardation Syndrome 2

Human phenotypes related to Hyperphosphatasia with Mental Retardation Syndrome 2:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 occasional (7.5%) HP:0000252
2 atrial septal defect 31 occasional (7.5%) HP:0001631
3 vesicoureteral reflux 31 occasional (7.5%) HP:0000076
4 ventriculomegaly 31 occasional (7.5%) HP:0002119
5 anterior plagiocephaly 31 occasional (7.5%) HP:0011326
6 seizure 31 occasional (7.5%) HP:0001250
7 intellectual disability 31 HP:0001249
8 hearing impairment 31 HP:0000365
9 hypertelorism 31 HP:0000316
10 wide nasal bridge 31 HP:0000431
11 delayed speech and language development 31 HP:0000750
12 short nose 31 HP:0003196
13 cleft palate 31 HP:0000175
14 growth delay 31 HP:0001510
15 upslanted palpebral fissure 31 HP:0000582
16 anal atresia 31 HP:0002023
17 aganglionic megacolon 31 HP:0002251
18 tented upper lip vermilion 31 HP:0010804
19 anal stenosis 31 HP:0002025
20 broad nasal tip 31 HP:0000455
21 generalized hypotonia 31 HP:0001290
22 long palpebral fissure 31 HP:0000637
23 shortening of all distal phalanges of the fingers 31 HP:0006118
24 elevated alkaline phosphatase 31 HP:0003155
25 broad hallux 31 HP:0010055

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
delayed speech and language development
hypotonia
delayed psychomotor development, moderate to severe
enlarged ventricles (1 patient)

Head And Neck Eyes:
hypertelorism
upslanting palpebral fissures
long palpebral fissures

Head And Neck Mouth:
cleft palate
tented mouth

Abdomen Gastrointestinal:
anal atresia
anal stenosis
megacolon

Skeletal Feet:
brachytelephalangy
broad halluces

Head And Neck Head:
microcephaly (in some patients)

Skeletal Skull:
plagiocephaly (1 patient)
coronal synostosis (1 patient)

Skin Nails Hair Nails:
hypoplastic or absent nails

Head And Neck Ears:
hearing impairment

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

Cardiovascular Heart:
atrial septal defect
heart defects

Skeletal Hands:
brachytelephalangy

Laboratory Abnormalities:
increased serum alkaline phosphatase
hyperphosphatasia

Growth Other:
poor growth

Genitourinary Bladder:
vesicoureteral reflux (1 patient)

Clinical features from OMIM®:

614749 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hyperphosphatasia with Mental Retardation Syndrome 2

Search Clinical Trials , NIH Clinical Center for Hyperphosphatasia with Mental Retardation Syndrome 2

Genetic Tests for Hyperphosphatasia with Mental Retardation Syndrome 2

Genetic tests related to Hyperphosphatasia with Mental Retardation Syndrome 2:

# Genetic test Affiliating Genes
1 Hyperphosphatasia with Mental Retardation Syndrome 2 29 PIGO

Anatomical Context for Hyperphosphatasia with Mental Retardation Syndrome 2

MalaCards organs/tissues related to Hyperphosphatasia with Mental Retardation Syndrome 2:

40
Heart

Publications for Hyperphosphatasia with Mental Retardation Syndrome 2

Articles related to Hyperphosphatasia with Mental Retardation Syndrome 2:

# Title Authors PMID Year
1
Mutations in PIGO, a member of the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation. 6 57
22683086 2012
2
Exome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey. 6
30109123 2018
3
PIGO deficiency: palmoplantar keratoderma and novel mutations. 6
28545593 2017
4
PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels. 6
24417746 2014

Variations for Hyperphosphatasia with Mental Retardation Syndrome 2

ClinVar genetic disease variations for Hyperphosphatasia with Mental Retardation Syndrome 2:

6 (show top 50) (show all 369)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIGO NM_032634.4(PIGO):c.2869C>T (p.Leu957Phe) SNV Pathogenic 35599 rs142164373 GRCh37: 9:35090263-35090263
GRCh38: 9:35090266-35090266
2 PIGO NM_032634.4(PIGO):c.1959G>A (p.Trp653Ter) SNV Pathogenic 565791 rs1391418639 GRCh37: 9:35091925-35091925
GRCh38: 9:35091928-35091928
3 PIGO NM_032634.4(PIGO):c.204dup (p.Arg69fs) Duplication Pathogenic 574401 rs751086453 GRCh37: 9:35095358-35095359
GRCh38: 9:35095361-35095362
4 PIGO NM_032634.4(PIGO):c.1269_1270TG[1] (p.Val424fs) Microsatellite Pathogenic 577203 rs1563998317 GRCh37: 9:35092612-35092613
GRCh38: 9:35092615-35092616
5 PIGO NM_032634.4(PIGO):c.2007G>A (p.Trp669Ter) SNV Pathogenic 581964 rs1563996824 GRCh37: 9:35091877-35091877
GRCh38: 9:35091880-35091880
6 PIGO NM_032634.4(PIGO):c.91dup (p.Thr31fs) Duplication Pathogenic 645706 rs1587178357 GRCh37: 9:35095471-35095472
GRCh38: 9:35095474-35095475
7 PIGO NM_032634.4(PIGO):c.511G>T (p.Gly171Ter) SNV Pathogenic 647724 rs1247927038 GRCh37: 9:35095052-35095052
GRCh38: 9:35095055-35095055
8 PIGO NM_032634.4(PIGO):c.438del (p.Phe146fs) Deletion Pathogenic 656785 rs1587176440 GRCh37: 9:35095125-35095125
GRCh38: 9:35095128-35095128
9 PIGO NM_032634.4(PIGO):c.196C>T (p.Arg66Ter) SNV Pathogenic 651005 rs763992668 GRCh37: 9:35095367-35095367
GRCh38: 9:35095370-35095370
10 PIGO NM_032634.4(PIGO):c.1549del (p.Ala517fs) Deletion Pathogenic 655474 rs1587166550 GRCh37: 9:35092335-35092335
GRCh38: 9:35092338-35092338
11 PIGO NM_032634.4(PIGO):c.590del (p.Pro197fs) Deletion Pathogenic 851969 GRCh37: 9:35094278-35094278
GRCh38: 9:35094281-35094281
12 PIGO NM_032634.4(PIGO):c.2191del (p.Arg731fs) Deletion Pathogenic 852858 GRCh37: 9:35091693-35091693
GRCh38: 9:35091696-35091696
13 PIGO NM_032634.4(PIGO):c.1187del (p.Leu396fs) Deletion Pathogenic 836206 GRCh37: 9:35092697-35092697
GRCh38: 9:35092700-35092700
14 PIGO NM_032634.4(PIGO):c.2921del (p.Gln974fs) Deletion Pathogenic 953680 GRCh37: 9:35090211-35090211
GRCh38: 9:35090214-35090214
15 PIGO NM_032634.4(PIGO):c.135dup (p.Gly46fs) Duplication Pathogenic 954297 GRCh37: 9:35095427-35095428
GRCh38: 9:35095430-35095431
16 PIGO NM_032634.4(PIGO):c.178del (p.Ala60fs) Deletion Pathogenic 963282 GRCh37: 9:35095385-35095385
GRCh38: 9:35095388-35095388
17 PIGO NM_032634.4(PIGO):c.2725C>T (p.Gln909Ter) SNV Pathogenic 952288 GRCh37: 9:35090592-35090592
GRCh38: 9:35090595-35090595
18 PIGO NM_032634.4(PIGO):c.163C>T (p.Gln55Ter) SNV Pathogenic 984635 GRCh37: 9:35095400-35095400
GRCh38: 9:35095403-35095403
19 PIGO NM_032634.3(PIGO):c.2361dupC Duplication Pathogenic 35600 rs770591449 GRCh37: 9:35091522-35091523
GRCh38: 9:35091525-35091526
20 overlap with 39 genes NC_000009.11:g.(?_34458984)_(35809462_?)del Deletion Pathogenic 583851 GRCh37: 9:34458984-35809462
GRCh38:
21 PIGO NM_032634.4(PIGO):c.1810dup (p.Arg604fs) Duplication Pathogenic 286126 rs774508288 GRCh37: 9:35092073-35092074
GRCh38: 9:35092076-35092077
22 PIGO NM_032634.4(PIGO):c.2404C>T (p.Arg802Ter) SNV Pathogenic 620478 rs1199247059 GRCh37: 9:35091480-35091480
GRCh38: 9:35091483-35091483
23 PIGO NM_032634.4(PIGO):c.2191dup (p.Arg731fs) Duplication Pathogenic/Likely pathogenic 574404 rs760848629 GRCh37: 9:35091692-35091693
GRCh38: 9:35091695-35091696
24 PIGO NM_032634.4(PIGO):c.1176_1186del (p.Glu392fs) Deletion Likely pathogenic 931654 GRCh37: 9:35092698-35092708
GRCh38: 9:35092701-35092711
25 PIGO NM_032634.4(PIGO):c.2854+1G>A SNV Likely pathogenic 989246 GRCh37: 9:35090462-35090462
GRCh38: 9:35090465-35090465
26 PIGO NM_032634.4(PIGO):c.2825A>C (p.Asn942Thr) SNV Likely pathogenic 984636 GRCh37: 9:35090492-35090492
GRCh38: 9:35090495-35090495
27 PIGO NM_032634.4(PIGO):c.1392delinsGA (p.Ile464fs) Indel Likely pathogenic 690299 rs1587167234 GRCh37: 9:35092492-35092492
GRCh38: 9:35092495-35092495
28 PIGO NM_032634.4(PIGO):c.3069+2T>C SNV Likely pathogenic 422406 rs1064795758 GRCh37: 9:35090061-35090061
GRCh38: 9:35090064-35090064
29 PIGO NM_032634.4(PIGO):c.2648-1G>A SNV Likely pathogenic 451522 rs755750516 GRCh37: 9:35090670-35090670
GRCh38: 9:35090673-35090673
30 PIGO NM_032634.4(PIGO):c.364C>T (p.Arg122Ter) SNV Conflicting interpretations of pathogenicity 421377 rs375682284 GRCh37: 9:35095199-35095199
GRCh38: 9:35095202-35095202
31 PIGO NM_032634.4(PIGO):c.2166G>C (p.Ala722=) SNV Conflicting interpretations of pathogenicity 366756 rs147101825 GRCh37: 9:35091718-35091718
GRCh38: 9:35091721-35091721
32 PIGO NM_032634.4(PIGO):c.2854+7C>A SNV Conflicting interpretations of pathogenicity 388945 rs768338180 GRCh37: 9:35090456-35090456
GRCh38: 9:35090459-35090459
33 PIGO NM_032634.4(PIGO):c.3118G>A (p.Val1040Ile) SNV Conflicting interpretations of pathogenicity 366753 rs149439295 GRCh37: 9:35089399-35089399
GRCh38: 9:35089402-35089402
34 PIGO NM_032634.4(PIGO):c.3141-9T>A SNV Conflicting interpretations of pathogenicity 507051 rs374227554 GRCh37: 9:35089227-35089227
GRCh38: 9:35089230-35089230
35 PIGO NM_032634.4(PIGO):c.590C>T (p.Pro197Leu) SNV Conflicting interpretations of pathogenicity 418409 rs150734953 GRCh37: 9:35094278-35094278
GRCh38: 9:35094281-35094281
36 PIGO NM_032634.4(PIGO):c.626A>G (p.Asn209Ser) SNV Conflicting interpretations of pathogenicity 366761 rs138028827 GRCh37: 9:35094242-35094242
GRCh38: 9:35094245-35094245
37 PIGO NM_032634.4(PIGO):c.468C>T (p.His156=) SNV Conflicting interpretations of pathogenicity 366762 rs374876329 GRCh37: 9:35095095-35095095
GRCh38: 9:35095098-35095098
38 PIGO NM_032634.4(PIGO):c.1416A>T (p.Ala472=) SNV Conflicting interpretations of pathogenicity 779701 rs749630366 GRCh37: 9:35092468-35092468
GRCh38: 9:35092471-35092471
39 PIGO NM_032634.4(PIGO):c.1758C>T (p.Val586=) SNV Conflicting interpretations of pathogenicity 473217 rs144103228 GRCh37: 9:35092126-35092126
GRCh38: 9:35092129-35092129
40 PIGO NM_032634.4(PIGO):c.969T>G (p.Leu323=) SNV Conflicting interpretations of pathogenicity 385746 rs142658052 GRCh37: 9:35093177-35093177
GRCh38: 9:35093180-35093180
41 PIGO NM_032634.4(PIGO):c.3070-12C>G SNV Uncertain significance 366754 rs199864376 GRCh37: 9:35089459-35089459
GRCh38: 9:35089462-35089462
42 PIGO NM_032634.4(PIGO):c.1991G>A (p.Arg664Gln) SNV Uncertain significance 652206 rs371923881 GRCh37: 9:35091893-35091893
GRCh38: 9:35091896-35091896
43 PIGO NM_032634.4(PIGO):c.79G>A (p.Gly27Ser) SNV Uncertain significance 989247 GRCh37: 9:35095484-35095484
GRCh38: 9:35095487-35095487
44 PIGO NM_032634.4(PIGO):c.449G>T (p.Gly150Val) SNV Uncertain significance 694579 rs1587176408 GRCh37: 9:35095114-35095114
GRCh38: 9:35095117-35095117
45 overlap with 39 genes NC_000009.11:g.(?_34458984)_(35809462_?)dup Duplication Uncertain significance 473211 GRCh37: 9:34458984-35809462
GRCh38:
46 PIGO NM_032634.4(PIGO):c.1396C>G (p.Leu466Val) SNV Uncertain significance 953186 GRCh37: 9:35092488-35092488
GRCh38: 9:35092491-35092491
47 PIGO NM_032634.4(PIGO):c.2326A>G (p.Thr776Ala) SNV Uncertain significance 953474 GRCh37: 9:35091558-35091558
GRCh38: 9:35091561-35091561
48 PIGO NM_032634.4(PIGO):c.1510A>G (p.Ile504Val) SNV Uncertain significance 963829 GRCh37: 9:35092374-35092374
GRCh38: 9:35092377-35092377
49 PIGO NM_032634.4(PIGO):c.237A>G (p.Arg79=) SNV Uncertain significance 966480 GRCh37: 9:35095326-35095326
GRCh38: 9:35095329-35095329
50 PIGO NM_032634.4(PIGO):c.890C>G (p.Ala297Gly) SNV Uncertain significance 967372 GRCh37: 9:35093467-35093467
GRCh38: 9:35093470-35093470

UniProtKB/Swiss-Prot genetic disease variations for Hyperphosphatasia with Mental Retardation Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 PIGO p.Leu957Phe VAR_068809 rs142164373
2 PIGO p.Arg119Trp VAR_079410 rs757441073
3 PIGO p.Asn370Ser VAR_079413 rs121410426
4 PIGO p.Lys1047Glu VAR_079416

Expression for Hyperphosphatasia with Mental Retardation Syndrome 2

Search GEO for disease gene expression data for Hyperphosphatasia with Mental Retardation Syndrome 2.

Pathways for Hyperphosphatasia with Mental Retardation Syndrome 2

GO Terms for Hyperphosphatasia with Mental Retardation Syndrome 2

Sources for Hyperphosphatasia with Mental Retardation Syndrome 2

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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