GPIBD1
MCID: GLY112
MIFTS: 33

Glycosylphosphatidylinositol Biosynthesis Defect 1 (GPIBD1)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Glycosylphosphatidylinositol Biosynthesis Defect 1

MalaCards integrated aliases for Glycosylphosphatidylinositol Biosynthesis Defect 1:

Name: Glycosylphosphatidylinositol Biosynthesis Defect 1 57 73
Glycosylphosphatidylinositol Deficiency 57 73 13 6 39
Gpibd1 57 73
Gpid 57 73
Hypercoagulability Syndrome Due to Glycosylphosphatidylinositol Deficiency 58
Congenital Disorder of Glycosylation Due to Pigm Deficiency 58
Portal Hypertension with Seizures and/or Macrocephaly 57
Glycosylphosphatidylinositol Deficiency; Gpid 57
Pigm-Cdg 58

Characteristics:

Orphanet epidemiological data:

58
hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
onset of thrombosis by age 2 years


HPO:

31
glycosylphosphatidylinositol biosynthesis defect 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Rare haematological diseases


Summaries for Glycosylphosphatidylinositol Biosynthesis Defect 1

OMIM® : 57 Glycosylphosphatidylinositol is a glycolipid that anchors more than 150 proteins to the cell surface, and these proteins, termed GPI-anchored proteins (GPI-APs), perform a variety of functions as enzymes, adhesion molecules, complement regulators, and coreceptors in signal transduction pathways. Reduced surface levels of GPI-APs or abnormal GPI-AP structure can therefore result in variable manifestations. Glycosylphosphatidylinositol biosynthesis defect-1 (GPIBD1) is characterized predominantly by portal hypertension due to portal vein thrombosis. Most patients have absence seizures, cerebral thrombosis, and macrocephaly. Some patients have mildly to moderately impaired intellectual development (summary by Makrythanasis et al., 2016; Pode-Shakked et al., 2019). (610293) (Updated 05-Mar-2021)

MalaCards based summary : Glycosylphosphatidylinositol Biosynthesis Defect 1, also known as glycosylphosphatidylinositol deficiency, is related to hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency and glucose phosphate isomerase deficiency. An important gene associated with Glycosylphosphatidylinositol Biosynthesis Defect 1 is PIGM (Phosphatidylinositol Glycan Anchor Biosynthesis Class M), and among its related pathways/superpathways are Post-translational modification- synthesis of GPI-anchored proteins and Glycosylphosphatidylinositol (GPI)-anchor biosynthesis. Related phenotypes are splenomegaly and hepatomegaly

UniProtKB/Swiss-Prot : 73 Glycosylphosphatidylinositol biosynthesis defect 1: An autosomal recessive disorder characterized by portal vein thrombosis and portal hypertension, absence seizures, macrocephaly, splenomegaly, cytopenias and early-onset cerebral infarctions.

Related Diseases for Glycosylphosphatidylinositol Biosynthesis Defect 1

Diseases in the Glycosylphosphatidylinositol Biosynthesis Defect 1 family:

Glycosylphosphatidylinositol Biosynthesis Defect 11 Glycosylphosphatidylinositol Biosynthesis Defect 15
Glycosylphosphatidylinositol Biosynthesis Defect 16 Glycosylphosphatidylinositol Biosynthesis Defect 17
Glycosylphosphatidylinositol Biosynthesis Defect 18

Diseases related to Glycosylphosphatidylinositol Biosynthesis Defect 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency 31.6 PIGW PIGM
2 glucose phosphate isomerase deficiency 11.0
3 hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency 11.0
4 hyperphosphatasia with mental retardation syndrome 1 10.8
5 coloboma, congenital heart disease, ichthyosiform dermatosis, mental retardation, and ear anomalies syndrome 10.8
6 multiple congenital anomalies-hypotonia-seizures syndrome 2 10.8
7 multiple congenital anomalies-hypotonia-seizures syndrome 1 10.8
8 hyperphosphatasia with mental retardation syndrome 3 10.8
9 hyperphosphatasia with mental retardation syndrome 2 10.8
10 multiple congenital anomalies-hypotonia-seizures syndrome 3 10.8
11 hyperphosphatasia with mental retardation syndrome 4 10.8
12 mental retardation, autosomal recessive 42 10.8
13 glycosylphosphatidylinositol biosynthesis defect 11 10.8
14 hyperphosphatasia with mental retardation syndrome 6 10.8
15 mental retardation, autosomal recessive 53 10.8
16 developmental and epileptic encephalopathy 38 10.8
17 developmental and epileptic encephalopathy 55 10.8
18 glycosylphosphatidylinositol biosynthesis defect 15 10.8
19 glycosylphosphatidylinositol biosynthesis defect 17 10.8
20 glycosylphosphatidylinositol biosynthesis defect 18 10.8
21 multiple congenital anomalies-hypotonia-seizures syndrome 4 10.8
22 developmental and epileptic encephalopathy 80 10.8
23 neurodevelopmental disorder with brain anomalies, seizures, and scoliosis 10.8
24 neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 10.8
25 hypotonia 10.0
26 ataxia and polyneuropathy, adult-onset 9.9
27 alacrima, achalasia, and mental retardation syndrome 9.9
28 west syndrome 9.9
29 autosomal recessive disease 9.9
30 paroxysmal nocturnal hemoglobinuria 9.9
31 hemoglobinuria 9.9
32 pathologic nystagmus 9.9
33 congenital disorders of n-linked glycosylation and multiple pathway 9.9
34 seizure disorder 9.9
35 hyperphosphatasia-intellectual disability syndrome 9.9
36 multiple congenital anomalies-hypotonia-seizures syndrome 9.6 PIGW PIGM
37 anterior segment dysgenesis 4 9.5 PIGW PIGM

Graphical network of the top 20 diseases related to Glycosylphosphatidylinositol Biosynthesis Defect 1:



Diseases related to Glycosylphosphatidylinositol Biosynthesis Defect 1

Symptoms & Phenotypes for Glycosylphosphatidylinositol Biosynthesis Defect 1

Human phenotypes related to Glycosylphosphatidylinositol Biosynthesis Defect 1:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 HP:0001744
2 hepatomegaly 31 HP:0002240
3 portal hypertension 31 HP:0001409
4 venous thrombosis 31 HP:0004936
5 portal vein thrombosis 31 HP:0030242
6 atonic seizure 31 HP:0010819
7 hepatic vein thrombosis 31 HP:0030243
8 seizure 31 HP:0001250
9 generalized non-motor (absence) seizure 31 HP:0002121
10 reduced granulocyte cd59 level 31 HP:0031555

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Abdomen Spleen:
splenomegaly

Cardiovascular Vascular:
portal hypertension
venous thrombosis
dilated superficial facial and abdominal veins (in some patients)

Neurologic Central Nervous System:
cerebellar atrophy (in some patients)
cerebral atrophy (in some patients)
seizures, absence
seizures, atonic
cerebral infarcts (in some patients)

Laboratory Abnormalities:
decreased expression of glycosylphosphatidylinositol-linked proteins (e.g., cd59 ) on hematopoietic cells

Abdomen Liver:
hepatomegaly
portal hypertension
portal vein thrombosis
hepatic venous thrombosis

Hematology:
thrombocytopenia

Head And Neck Head:
macrocephaly (in some patients)

Clinical features from OMIM®:

610293 (Updated 05-Mar-2021)

Drugs & Therapeutics for Glycosylphosphatidylinositol Biosynthesis Defect 1

Search Clinical Trials , NIH Clinical Center for Glycosylphosphatidylinositol Biosynthesis Defect 1

Genetic Tests for Glycosylphosphatidylinositol Biosynthesis Defect 1

Anatomical Context for Glycosylphosphatidylinositol Biosynthesis Defect 1

Publications for Glycosylphosphatidylinositol Biosynthesis Defect 1

Articles related to Glycosylphosphatidylinositol Biosynthesis Defect 1:

(show all 12)
# Title Authors PMID Year
1
Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiency. 6 57 61
16767100 2006
2
Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation. 57 6
31445883 2019
3
Targeted therapy for inherited GPI deficiency. 6 57
17442906 2007
4
Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia. 57
26996948 2016
5
Cell-type-specific transcriptional regulation of PIGM underpins the divergent hematologic phenotype in inherited GPl deficiency. 6
25293775 2014
6
Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models. 61
33607654 2021
7
PIGW-related glycosylphosphatidylinositol deficiency: Description of a new patient and review of the literature. 61
32198969 2020
8
CNS glycosylphosphatidylinositol deficiency results in delayed white matter development, ataxia and premature death in a novel mouse model. 61
32179897 2020
9
Clinical variability in inherited glycosylphosphatidylinositol deficiency disorders. 61
30054924 2019
10
A novel mutation in PIGW causes glycosylphosphatidylinositol deficiency without hyperphosphatasia. 61
27626616 2016
11
A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency. 61
26419326 2016
12
Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome. 61
22228761 2012

Variations for Glycosylphosphatidylinositol Biosynthesis Defect 1

ClinVar genetic disease variations for Glycosylphosphatidylinositol Biosynthesis Defect 1:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PIGM NM_145167.2(PIGM):c.-270C>G SNV Pathogenic 1288 rs587776528 1:160001799-160001799 1:160032009-160032009
2 PIGM NM_145167.3(PIGM):c.1252_1253GA[1] (p.Arg419fs) Microsatellite Uncertain significance 503728 rs755366154 1:160000273-160000276 1:160030483-160030486
3 PIGM NM_145167.3(PIGM):c.104A>G (p.Tyr35Cys) SNV Uncertain significance 972028 1:160001426-160001426 1:160031636-160031636
4 PIGW NM_001346754.2(PIGW):c.608T>G (p.Leu203Trp) SNV Uncertain significance 634642 rs12952744 17:34893558-34893558 17:36537709-36537709
5 PIGM NM_145167.3(PIGM):c.950G>A (p.Cys317Tyr) SNV Uncertain significance 640196 rs138769872 1:160000580-160000580 1:160030790-160030790
6 PIGM NC_000001.11:g.(?_160030448)_(160032009_?)del Deletion Uncertain significance 641554 1:160000238-160001799 1:160030448-160032009
7 PIGM NM_145167.3(PIGM):c.238C>G (p.Leu80Val) SNV Uncertain significance 665365 rs945112516 1:160001292-160001292 1:160031502-160031502
8 PIGM NM_145167.3(PIGM):c.582G>T (p.Leu194=) SNV Benign 775618 rs35060029 1:160000948-160000948 1:160031158-160031158
9 PIGM NM_145167.3(PIGM):c.6C>T (p.Gly2=) SNV Benign 592292 rs61757715 1:160001524-160001524 1:160031734-160031734
10 PIGM NM_145167.3(PIGM):c.819G>A (p.Pro273=) SNV Benign 193498 rs138151842 1:160000711-160000711 1:160030921-160030921

Expression for Glycosylphosphatidylinositol Biosynthesis Defect 1

Search GEO for disease gene expression data for Glycosylphosphatidylinositol Biosynthesis Defect 1.

Pathways for Glycosylphosphatidylinositol Biosynthesis Defect 1

Pathways related to Glycosylphosphatidylinositol Biosynthesis Defect 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.95 PIGW PIGM
2
Show member pathways
10.24 PIGW PIGM

GO Terms for Glycosylphosphatidylinositol Biosynthesis Defect 1

Cellular components related to Glycosylphosphatidylinositol Biosynthesis Defect 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 8.62 PIGW PIGM

Biological processes related to Glycosylphosphatidylinositol Biosynthesis Defect 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GPI anchor biosynthetic process GO:0006506 8.96 PIGW PIGM
2 preassembly of GPI anchor in ER membrane GO:0016254 8.62 PIGW PIGM

Sources for Glycosylphosphatidylinositol Biosynthesis Defect 1

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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