MCID: OST131
MIFTS: 43

Osteopetrosis, Autosomal Dominant 2

Categories: Genetic diseases, Rare diseases, Eye diseases, Bone diseases, Fetal diseases, Nephrological diseases, Neuronal diseases, Blood 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
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
Autosomal Dominant Osteopetrosis 2 12
Marble Disease Autosomal Dominant 75
Marble Bones, Autosomal Dominant 57
Albers-Schonberg Osteopetrosis 12
Albers-Schönberg Osteopetrosis 59
Osteopetrosis 73

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 and bone disease. An important gene associated with Osteopetrosis, Autosomal Dominant 2 is CLCN7 (Chloride Voltage-Gated Channel 7), and among its related pathways/superpathways are Parathyroid hormone synthesis, secretion and action and Transcription_Role of VDR in regulation of genes involved in osteoporosis. The drugs Adenosine and interferons have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and eye, and related phenotypes are hydrocephalus and macrocephaly

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 sclerosis, predominantly involving the spine, the pelvis, and the skull base. Fragility of bones and dental abscess are leading complications. Autosomal dominant osteopetrosis-1 (OPTA1; 607634) 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. (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

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

GenomeRNAi Phenotypes related to Osteopetrosis, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.4 BGLAP
2 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.4 BGLAP
3 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.4 BGLAP
4 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.4 BGLAP TNFSF11
5 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.4 BGLAP
6 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.4 BGLAP
7 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.4 BGLAP
8 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.4 BGLAP
9 Increased shRNA abundance (Z-score > 2) GR00366-A-174 9.4 TNFSF11
10 Increased shRNA abundance (Z-score > 2) GR00366-A-178 9.4 BGLAP
11 Increased shRNA abundance (Z-score > 2) GR00366-A-46 9.4 TNFSF11

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 interferons Phase 2
3 Anti-Infective Agents Phase 2
4 Interferon-gamma Phase 2
5 Antiviral Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Use of ACTIMMUNE in Patients With ADO2 Recruiting NCT02584608 Phase 2 ACTIMMUNE

Search NIH Clinical Center for Osteopetrosis, Autosomal Dominant 2

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


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

Publications for Osteopetrosis, Autosomal Dominant 2

Articles related to Osteopetrosis, Autosomal Dominant 2:

# Title Authors Year
1
Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. ( 11741829 )
2001

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

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

# Super pathways Score Top Affiliating Genes
1 11.28 BGLAP TNFSF11
2 10.81 BGLAP TNFSF11
3 10.55 BGLAP TNFSF11
4 9.77 BGLAP TNFSF11

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 ossification GO:0001503 9.16 BGLAP TNFSF11
2 bone development GO:0060348 8.96 BGLAP TNFSF11
3 regulation of osteoclast differentiation GO:0045670 8.62 BGLAP 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
Content
Loading form....