OPTA1
MCID: OST125
MIFTS: 34

Osteopetrosis, Autosomal Dominant 1 (OPTA1)

Categories: Blood diseases, Bone diseases, Cancer diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Liver diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Osteopetrosis, Autosomal Dominant 1

MalaCards integrated aliases for Osteopetrosis, Autosomal Dominant 1:

Name: Osteopetrosis, Autosomal Dominant 1 57 72 13 70
Autosomal Dominant Osteopetrosis 1 12 29 6 15
Opta1 57 12 20 72
Autosomal Dominant Osteopetrosis Type 1 12 20 58
Osteopetrosis Autosomal Dominant Type 1 20 44
Osteopetrosis, Autosomal Dominant, Type I 57
Osteopetrosis, Autosomal Dominant, Type 1 39

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant osteopetrosis type 1
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: normal life expectancy;

OMIM®:

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

Miscellaneous:
genetic heterogeneity (see )
progressive sclerosis with age
allelic to osteoporosis-pseudoglioma syndrome , van buchem type 2 , high bone mass , autosomal dominant endosteal hyperostosis


HPO:

31
osteopetrosis, autosomal dominant 1:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0110937
OMIM® 57 607634
OMIM Phenotypic Series 57 PS607634
MESH via Orphanet 45 C536056
ICD10 via Orphanet 33 Q78.2
UMLS via Orphanet 71 C1843330 C2931097
Orphanet 58 ORPHA2783
MedGen 41 C1843330
UMLS 70 C1843330

Summaries for Osteopetrosis, Autosomal Dominant 1

GARD : 20 Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth. Symptoms and severity can vary greatly, ranging from neonatal onset with life-threatening complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray. Depending on severity and age of onset, features may include fractures, short stature, compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures, and life-threatening pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by mutations in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive. Management depends on the specific symptoms and severity and may include vitamin D supplements, various medications, and/or surgery. Adult osteopetrosis requires no treatment by itself, but complications may require intervention.

MalaCards based summary : Osteopetrosis, Autosomal Dominant 1, also known as autosomal dominant osteopetrosis 1, is related to osteopetrosis, autosomal dominant 2 and osteopetrosis, autosomal dominant 3, and has symptoms including headache An important gene associated with Osteopetrosis, Autosomal Dominant 1 is LRP5 (LDL Receptor Related Protein 5). Affiliated tissues include bone and bone marrow, and related phenotypes are thickened calvaria and conductive hearing impairment

Disease Ontology : 12 An osteopetrosis characterized by autosomal dominant inheritance of generalized osteosclerosis that is most pronounced in the cranial vault, absence of increased fractures and has material basis in heterozygous mutation in the LRP5 gene on chromosome 11q13.

OMIM® : 57 The osteopetroses are a heterogeneous group of genetic disorders characterized by increased bone density due to impaired bone resorption by osteoclasts. Autosomal dominant osteopetrosis-1 is characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate (summary by Van Hul et al., 2002). (607634) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Osteopetrosis, autosomal dominant 1: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate.

Related Diseases for Osteopetrosis, Autosomal Dominant 1

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Dominant 1:



Diseases related to Osteopetrosis, Autosomal Dominant 1

Symptoms & Phenotypes for Osteopetrosis, Autosomal Dominant 1

Human phenotypes related to Osteopetrosis, Autosomal Dominant 1:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 thickened calvaria 31 HP:0002684
2 conductive hearing impairment 31 HP:0000405
3 abnormality of pelvic girdle bone morphology 31 HP:0002644
4 abnormality of the vertebral column 31 HP:0000925
5 headache 31 HP:0002315
6 generalized osteosclerosis 31 HP:0005789
7 osteopetrosis 31 HP:0011002

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
headache

Skeletal Skull:
thickened cranial vault
pronounced calvarial sclerosis

Skeletal Spine:
no 'rugger-jersey spine'
variable sclerosis

Laboratory Abnormalities:
normal serum acid phosphatase

Head And Neck Ears:
conductive hearing loss

Skeletal:
diffuse, symmetrical osteosclerosis
no increased fracture rate

Skeletal Pelvis:
no endobones

Clinical features from OMIM®:

607634 (Updated 05-Apr-2021)

UMLS symptoms related to Osteopetrosis, Autosomal Dominant 1:


headache

Drugs & Therapeutics for Osteopetrosis, Autosomal Dominant 1

Search Clinical Trials , NIH Clinical Center for Osteopetrosis, Autosomal Dominant 1

Cochrane evidence based reviews: osteopetrosis autosomal dominant type 1

Genetic Tests for Osteopetrosis, Autosomal Dominant 1

Genetic tests related to Osteopetrosis, Autosomal Dominant 1:

# Genetic test Affiliating Genes
1 Autosomal Dominant Osteopetrosis 1 29 LRP5

Anatomical Context for Osteopetrosis, Autosomal Dominant 1

MalaCards organs/tissues related to Osteopetrosis, Autosomal Dominant 1:

40
Bone, Bone Marrow

Publications for Osteopetrosis, Autosomal Dominant 1

Articles related to Osteopetrosis, Autosomal Dominant 1:

(show all 18)
# Title Authors PMID Year
1
Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. 57 6
12579474 2003
2
Molecular genetics of too much bone. 57
12351574 2002
3
Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13. 57
12054167 2002
4
High bone density due to a mutation in LDL-receptor-related protein 5. 6
12015390 2002
5
A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. 6
11741193 2002
6
[Van Buchem disease. Maxillofacial changes, diagnostic classification and general principles of treatment]. 6
10434540 1999
7
Autosomal dominant osteopetrosis. 57
8358946 1993
8
Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis. 57
3377922 1988
9
Heterogeneity of autosomal dominant osteopetrosis. 57
3588909 1987
10
Suppressors of dGTP Starvation in Escherichia coli. 61
28373271 2017
11
Transcriptome Analysis of Escherichia coli during dGTP Starvation. 61
27002130 2016
12
[Autosomal dominant osteopetrosis: a presentation of 3 cases and a new gene mutation]. 61
24882046 2015
13
Structure and regulation of the gene for dGTP triphosphohydrolase from Escherichia coli. 61
2157212 1990
14
Escherichia coli dGTP triphosphohydrolase is inhibited by gene 1.2 protein of bacteriophage T7. 61
2843524 1988
15
A unique deoxyguanosine triphosphatase is responsible for the optA1 phenotype of Escherichia coli. 61
2833745 1988
16
Purification and characterization of the gene 1.2 protein of bacteriophage T7. 61
3494013 1987
17
Gene 1.2 protein of bacteriophage T7. Effect on deoxyribonucleotide pools. 61
3549718 1987
18
Genetic analysis of gene 1.2 of bacteriophage T7: isolation of a mutant of Escherichia coli unable to support the growth of T7 gene 1.2 mutants. 61
7012382 1981

Variations for Osteopetrosis, Autosomal Dominant 1

ClinVar genetic disease variations for Osteopetrosis, Autosomal Dominant 1:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LRP5 NM_002335.4(LRP5):c.511G>C (p.Gly171Arg) SNV Pathogenic 6281 rs121908669 GRCh37: 11:68125140-68125140
GRCh38: 11:68357672-68357672
2 LRP5 NM_002335.4(LRP5):c.758C>T (p.Thr253Ile) SNV Pathogenic 6285 rs121908673 GRCh37: 11:68131286-68131286
GRCh38: 11:68363818-68363818
3 LRP5 NM_002335.4(LRP5):c.640G>A (p.Ala214Thr) SNV Pathogenic 6283 rs121908671 GRCh37: 11:68125269-68125269
GRCh38: 11:68357801-68357801
4 LRP5 NM_002335.4(LRP5):c.724G>A (p.Ala242Thr) SNV Pathogenic 6282 rs121908670 GRCh37: 11:68131252-68131252
GRCh38: 11:68363784-68363784
5 LRP5 NM_002335.4(LRP5):c.3107G>A (p.Arg1036Gln) SNV Uncertain significance 183255 rs61889560 GRCh37: 11:68191036-68191036
GRCh38: 11:68423568-68423568
6 LRP5 NM_002335.4(LRP5):c.3107G>A (p.Arg1036Gln) SNV Uncertain significance 183255 rs61889560 GRCh37: 11:68191036-68191036
GRCh38: 11:68423568-68423568
7 LRP5 NM_002335.4(LRP5):c.1199C>T (p.Ala400Val) SNV Uncertain significance 520692 rs201320326 GRCh37: 11:68153967-68153967
GRCh38: 11:68386499-68386499

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Dominant 1:

72
# Symbol AA change Variation ID SNP ID
1 LRP5 p.Asp111Tyr VAR_021807
2 LRP5 p.Gly171Arg VAR_021808 rs121908669
3 LRP5 p.Ala242Thr VAR_021812 rs121908670
4 LRP5 p.Thr253Ile VAR_021813 rs121908673

Expression for Osteopetrosis, Autosomal Dominant 1

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Dominant 1.

Pathways for Osteopetrosis, Autosomal Dominant 1

GO Terms for Osteopetrosis, Autosomal Dominant 1

Cellular components related to Osteopetrosis, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ficolin-1-rich granule lumen GO:1904813 8.96 PNP DERA
2 secretory granule lumen GO:0034774 8.62 PNP DERA

Sources for Osteopetrosis, Autosomal Dominant 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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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