OPTA2
MCID: OST131
MIFTS: 53

Osteopetrosis, Autosomal Dominant 2 (OPTA2)

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

Aliases & Classifications for Osteopetrosis, Autosomal Dominant 2

MalaCards integrated aliases for Osteopetrosis, Autosomal Dominant 2:

Name: Osteopetrosis, Autosomal Dominant 2 57 75 13
Osteopetrosis Autosomal Dominant Type 2 12 53 59 29 6 73
Opta2 57 12 53 75
Autosomal Dominant Albers-Schonberg Disease 12 75
Osteopetrosis, Autosomal Dominant, Type Ii 57 55
Autosomal Dominant Osteopetrosis 2 12 15
Osteopetrosis 44 73
Albers-Schonberg Disease, Autosomal Dominant 57
Osteopetrosis, Autosomal Dominant, Type 2 40
Autosomal Dominant Osteopetrosis Type Ii 12
Autosomal Dominant Osteopetrosis Type 2 53
Osteosclerosis Fragilis Generalisata 57
Marble Disease Autosomal Dominant 75
Marble Bones, Autosomal Dominant 57
Albers-Schonberg Osteopetrosis 12
Albers-Schönberg Osteopetrosis 59

Characteristics:

Orphanet epidemiological data:

59
albers-schönberg osteopetrosis
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset in childhood
genetic heterogeneity (see )
progressive sclerosis with age
20-40% patients are asymptomatic
see recessive form optb4


HPO:

32
osteopetrosis, autosomal dominant 2:
Inheritance heterogeneous autosomal dominant inheritance
Onset and clinical course juvenile onset


Classifications:



Summaries for Osteopetrosis, Autosomal Dominant 2

NIH Rare Diseases : 53 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 2, also known as osteopetrosis autosomal dominant type 2, is related to osteopetrosis, autosomal recessive 6 and osteopetrosis, autosomal recessive 3. An important gene associated with Osteopetrosis, Autosomal Dominant 2 is CLCN7 (Chloride Voltage-Gated Channel 7), and among its related pathways/superpathways are Osteoclast differentiation and Lysosome. The drugs Adenosine and Anti-Infective Agents have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and eye, and related phenotypes are macrocephaly and joint dislocation

Disease Ontology : 12 An osteopetrosis characterized by autosomal dominant inheritance of sclerosis predominantly involving the spine, the pelvis, and the skull base, bone fragility and dental abscesses that has material basis in mutation in the CLCN7 gene on chromosome 16p13.

OMIM : 57 Autosomal dominant osteopetrosis-2 is characterized by segmentary osteosclerosis, predominantly at the vertebral endplates ('rugger-jersey spine'), iliac wings ('bone within bone' sign), and skull base. Clinical manifestations include cranial nerve palsies, mandibular osteomyelitis, osteoarthritis of the hip, and nontraumatic fractures, particularly of the long bones (Cleiren et al., 2001). OPTA2 accounts for 70% of cases of autosomal dominant osteopetrosis (Del Fattore et al., 2008). For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (607634). (166600)

UniProtKB/Swiss-Prot : 75 Osteopetrosis, autosomal dominant 2: 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. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. It is characterized by sclerosis, predominantly involving the spine, the pelvis and the skull base.

Related Diseases for Osteopetrosis, Autosomal Dominant 2

Diseases in the Osteopetrosis family:

Osteopetrosis, Autosomal Dominant 2 Osteopetrosis, Autosomal Recessive 1
Osteopetrosis, Autosomal Recessive 2 Osteopetrosis, Autosomal Recessive 5
Osteopetrosis, Autosomal Recessive 3 Osteopetrosis, Autosomal Dominant 1
Osteopetrosis, Autosomal Recessive 4 Osteopetrosis, Autosomal Recessive 6
Osteopetrosis, Autosomal Recessive 7 Osteopetrosis, Autosomal Recessive 8
Osteopetrosis, Autosomal Dominant 3 Clcn7-Related Osteopetrosis
Autosomal Recessive Malignant Osteopetrosis

Diseases related to Osteopetrosis, Autosomal Dominant 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 171)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis, autosomal recessive 6 34.4 TCIRG1 CLCN7
2 osteopetrosis, autosomal recessive 3 34.3 TCIRG1 CLCN7
3 osteopetrosis, autosomal recessive 2 34.3 TNFSF11 CLCN7
4 autosomal recessive malignant osteopetrosis 33.7 TNFSF11 TCIRG1 CLCN7
5 pycnodysostosis 32.4 CTSK CLCN7
6 osteomyelitis 31.0 TNFSF11 CTSK ACP5
7 endosteal hyperostosis, autosomal dominant 30.9 TNFSF11 TCIRG1 LRP5 CTSK CLCN7
8 osteopetrosis 30.7 TNFSF11 TCIRG1 LRP5 CTSK CLCN7
9 osteonecrosis 30.3 TNFSF11 BGLAP ACP5
10 bone disease 30.0 TNFSF11 SOST LRP5 CTSK CLCN7 BGLAP
11 bone resorption disease 30.0 TNFSF11 SOST LRP5 CTSK BGLAP ACP5
12 paget's disease of bone 29.8 TNFSF11 BGLAP ACP5
13 osteoporosis 29.6 TNFSF11 SOST LRP5 CTSK BGLAP ACP5
14 osteopetrosis, autosomal recessive 7 12.7
15 osteopetrosis, autosomal recessive 1 12.6
16 osteopetrosis, autosomal dominant 1 12.6
17 osteopetrosis, autosomal recessive 5 12.5
18 osteopetrosis, autosomal recessive 4 12.5
19 ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema 12.5
20 coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness 12.4
21 osteopetrosis, autosomal recessive 8 12.4
22 osteopetrosis, autosomal dominant 3 12.3
23 infantile osteopetrosis with neuroaxonal dysplasia 12.1
24 clcn7-related osteopetrosis 12.1
25 osteopetrosis and infantile neuroaxonal dystrophy 12.0
26 raine syndrome 11.3
27 dysosteosclerosis 11.3
28 trichodentoosseous syndrome 11.0
29 immunodeficiency 33 11.0
30 renal tubular acidosis 10.4
31 hematopoietic stem cell transplantation 10.3
32 rickets 10.3
33 villonodular synovitis 10.2 TNFSF11 ACP5
34 kummell's disease 10.2 TNFSF11 SOST
35 periapical periodontitis 10.2 TNFSF11 ACP5
36 impaired renal function disease 10.2 SOST BGLAP
37 mass syndrome 10.2 SOST LRP5
38 craniodiaphyseal dysplasia 10.2 SOST LRP5
39 hydrocephalus 10.2
40 leukemia 10.2
41 microphthalmia 10.2
42 pigmented villonodular synovitis 10.2 TNFSF11 ACP5
43 glucocorticoid-induced osteoporosis 10.1 TNFSF11 BGLAP ACP5
44 camurati-engelmann disease 10.1 LRP5 BGLAP ACP5
45 multicentric carpotarsal osteolysis syndrome 10.1 TNFSF11 CTSK BGLAP
46 osteoporosis, juvenile 10.1 SOST LRP5 BGLAP
47 sclerosteosis 2 10.1 SOST LRP5
48 giant cell tumor 10.1 TNFSF11 CTSK BGLAP
49 van buchem disease 10.1 SOST LRP5
50 mastocytosis 10.1

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Dominant 2:



Diseases related to Osteopetrosis, Autosomal Dominant 2

Symptoms & Phenotypes for Osteopetrosis, Autosomal Dominant 2

Symptoms via clinical synopsis from OMIM:

57
Skeletal Skull:
mandibular osteomyelitis
pronounced skull base sclerosis

Laboratory Abnormalities:
elevated serum acid phosphatase

Head And Neck Eyes:
vision loss, severe, beginning in childhood (12 of 62 patients)

Skeletal Spine:
'rugger-jersey' spine (vertebral endplate thickening)

Hematology:
bone marrow failure (in some patients)

Skeletal Pelvis:
hip osteoarthritis
endobones (bone within bone)

Head And Neck Face:
facial nerve palsy

Skeletal:
osteosclerosis, diffuse symmetrical
increased long bone fracture rate (75% of patients)
multiple fractures

Neurologic Peripheral Nervous System:
facial palsy due to cranial nerve vii compression


Clinical features from OMIM:

166600

Human phenotypes related to Osteopetrosis, Autosomal Dominant 2:

59 32 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000256
2 joint dislocation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001373
3 frontal bossing 59 32 hallmark (90%) Very frequent (99-80%) HP:0002007
4 osteoarthritis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002758
5 genu valgum 59 32 frequent (33%) Frequent (79-30%) HP:0002857
6 abnormality of epiphysis morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0005930
7 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
8 facial palsy 59 32 hallmark (90%) Very frequent (99-80%) HP:0010628
9 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
10 aseptic necrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0010885
11 carious teeth 59 32 occasional (7.5%) Occasional (29-5%) HP:0000670
12 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
13 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
14 blindness 59 32 occasional (7.5%) Occasional (29-5%) HP:0000618
15 anemia 59 32 frequent (33%) Frequent (79-30%) HP:0001903
16 generalized osteosclerosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0005789
17 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000944
18 abnormality of the metacarpal bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0001163
19 hypocalcemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002901
20 recurrent fractures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002757
21 bone pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002653
22 short distal phalanx of finger 59 32 hallmark (90%) Very frequent (99-80%) HP:0009882
23 mandibular osteomyelitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0007626
24 arthritis 59 Very frequent (99-80%)
25 abnormality of the dentition 59 Frequent (79-30%)
26 visual impairment 59 Frequent (79-30%)
27 cranial nerve paralysis 59 Very frequent (99-80%)
28 bone marrow hypocellularity 32 occasional (7.5%) HP:0005528
29 visual loss 32 HP:0000572
30 osteomyelitis 59 Very frequent (99-80%)
31 abnormality of pelvic girdle bone morphology 32 HP:0002644
32 abnormality of leukocytes 59 Occasional (29-5%)
33 osteopetrosis 32 HP:0011002
34 facial paralysis 32 HP:0007209
35 fractures of the long bones 32 HP:0003084
36 hip osteoarthritis 32 HP:0008843
37 abnormality of the vertebral endplates 32 HP:0005106
38 elevated serum acid phosphatase 32 HP:0003148
39 abnormal leukocyte morphology 32 occasional (7.5%) HP:0001881

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Dominant 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.02 CLCN7 CTSK IRF6 ITGB5 LRP5 SERPINE2
2 hematopoietic system MP:0005397 9.91 CLCN7 CTSK ITGB5 LRP5 SPHK1 TCIRG1
3 homeostasis/metabolism MP:0005376 9.9 CES1 CLCN7 CTSK LRP5 SERPINE2 SOST
4 craniofacial MP:0005382 9.8 CLCN7 CTSK IRF6 LRP5 TCIRG1 TNFSF11
5 limbs/digits/tail MP:0005371 9.56 CLCN7 CTSK IRF6 LRP5 SOST TCIRG1
6 skeleton MP:0005390 9.23 CLCN7 CTSK IRF6 LRP5 SOST TCIRG1

Drugs & Therapeutics for Osteopetrosis, Autosomal Dominant 2

Drugs for Osteopetrosis, Autosomal Dominant 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational Phase 2 58-61-7 60961
2 Anti-Infective Agents Phase 2
3 Interferon-gamma Phase 2
4 Antiviral Agents Phase 2
5 interferons Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Use of ACTIMMUNE in Patients With ADO2 Active, not recruiting NCT02584608 Phase 2 ACTIMMUNE

Search NIH Clinical Center for Osteopetrosis, Autosomal Dominant 2

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Cochrane evidence based reviews: osteopetrosis

Genetic Tests for Osteopetrosis, Autosomal Dominant 2

Genetic tests related to Osteopetrosis, Autosomal Dominant 2:

# Genetic test Affiliating Genes
1 Osteopetrosis Autosomal Dominant Type 2 29 CLCN7

Anatomical Context for Osteopetrosis, Autosomal Dominant 2

MalaCards organs/tissues related to Osteopetrosis, Autosomal Dominant 2:

41
Bone, Bone Marrow, Eye, Lung, Brain, Thyroid, Myeloid

Publications for Osteopetrosis, Autosomal Dominant 2

Articles related to Osteopetrosis, Autosomal Dominant 2:

# Title Authors Year
1
Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2. ( 27325559 )
2016

Variations for Osteopetrosis, Autosomal Dominant 2

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Dominant 2:

75
# Symbol AA change Variation ID SNP ID
1 CLCN7 p.Arg762Gln VAR_017838 rs121434433
2 CLCN7 p.Arg767Trp VAR_017840 rs121434435
3 CLCN7 p.Gly215Arg VAR_020997 rs397515539
4 CLCN7 p.Arg286Gln VAR_021000 rs760956030
5 CLCN7 p.Leu490Phe VAR_021003
6 CLCN7 p.Gly677Val VAR_021006
7 CLCN7 p.Phe318Leu VAR_064640
8 CLCN7 p.Phe758Leu VAR_064646 rs760740877

ClinVar genetic disease variations for Osteopetrosis, Autosomal Dominant 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CLCN7 NM_001287.5(CLCN7): c.2299C> T (p.Arg767Trp) single nucleotide variant Pathogenic rs121434435 GRCh37 Chromosome 16, 1497039: 1497039
2 CLCN7 NM_001287.5(CLCN7): c.2299C> T (p.Arg767Trp) single nucleotide variant Pathogenic rs121434435 GRCh38 Chromosome 16, 1447038: 1447038
3 CLCN7 CLCN7, 2-BP DEL, 2423AG deletion Pathogenic
4 CLCN7 NM_001287.5(CLCN7): c.296A> G (p.Tyr99Cys) single nucleotide variant Likely pathogenic rs387907576 GRCh37 Chromosome 16, 1511461: 1511461
5 CLCN7 NM_001287.5(CLCN7): c.296A> G (p.Tyr99Cys) single nucleotide variant Likely pathogenic rs387907576 GRCh38 Chromosome 16, 1461460: 1461460
6 CLCN7 NM_001287.5(CLCN7): c.857G> A (p.Arg286Gln) single nucleotide variant Pathogenic rs760956030 GRCh37 Chromosome 16, 1506173: 1506173
7 CLCN7 NM_001287.5(CLCN7): c.857G> A (p.Arg286Gln) single nucleotide variant Pathogenic rs760956030 GRCh38 Chromosome 16, 1456172: 1456172

Expression for Osteopetrosis, Autosomal Dominant 2

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Dominant 2.

Pathways for Osteopetrosis, Autosomal Dominant 2

GO Terms for Osteopetrosis, Autosomal Dominant 2

Biological processes related to Osteopetrosis, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 bone morphogenesis GO:0060349 9.32 ACP5 LRP5
2 osteoblast development GO:0002076 9.26 BGLAP LRP5
3 regulation of osteoclast differentiation GO:0045670 9.16 BGLAP TNFSF11
4 bone resorption GO:0045453 9.13 ACP5 CTSK TNFSF11
5 ossification GO:0001503 8.92 ACP5 BGLAP SOST TNFSF11

Sources for Osteopetrosis, Autosomal Dominant 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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