MCID: ATS282
MIFTS: 38

Autosomal Recessive Malignant Osteopetrosis

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Aliases & Classifications for Autosomal Recessive Malignant Osteopetrosis

MalaCards integrated aliases for Autosomal Recessive Malignant Osteopetrosis:

Name: Autosomal Recessive Malignant Osteopetrosis 58
Infantile Malignant Osteopetrosis 58 71

Characteristics:


Inheritance:

Autosomal recessive 58

Age Of Onset:

Infancy,Neonatal 58

Classifications:

Orphanet: 58  
Rare eye diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Autosomal Recessive Malignant Osteopetrosis

Orphanet: 58 Infantile malignant osteopetrosis is a rare congenital disorder of bone resorption characterised by generalised skeletal densification.

MalaCards based summary: Autosomal Recessive Malignant Osteopetrosis, also known as infantile malignant osteopetrosis, is related to osteopetrosis, autosomal recessive 5 and osteopetrosis, autosomal recessive 1. An important gene associated with Autosomal Recessive Malignant Osteopetrosis is CLCN7 (Chloride Voltage-Gated Channel 7), and among its related pathways/superpathways are Ion channel transport and Autosomal recessive osteopetrosis pathways. The drug Levoleucovorin has been mentioned in the context of this disorder. Affiliated tissues include bone, eye and skin, and related phenotypes are macrocephaly and nystagmus

Related Diseases for Autosomal Recessive Malignant Osteopetrosis

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 Autosomal Recessive Malignant Osteopetrosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 52)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis, autosomal recessive 5 32.1 TCIRG1 CLCN7
2 osteopetrosis, autosomal recessive 1 32.0 TCIRG1 CLCN7
3 osteopetrosis, autosomal recessive 4 31.7 TCIRG1 CLCN7
4 osteopetrosis, autosomal recessive 7 31.4 TCIRG1 CLCN7
5 bone disease 29.7 TNFSF11 CLCN7
6 endosteal hyperostosis, autosomal dominant 29.5 TNFSF11 TCIRG1 CLCN7
7 osteopetrosis 29.2 TNFSF11 TCIRG1 SNX10 CLCN7
8 graft-versus-host disease 10.3
9 thrombocytopenia 10.2
10 clcn7-related osteopetrosis 10.2
11 pulmonary hypertension, primary, 1 10.1
12 aplastic anemia 10.1
13 pancytopenia 10.1
14 pathologic nystagmus 10.1
15 silver-russell syndrome 1 10.0
16 strabismus 10.0
17 choroidal dystrophy, central areolar, 1 10.0
18 myelofibrosis 10.0
19 3-methylglutaconic aciduria, type iii 10.0
20 agammaglobulinemia, x-linked 10.0
21 juvenile myelomonocytic leukemia 10.0
22 choanal atresia, posterior 10.0
23 deficiency anemia 10.0
24 pulmonary hypertension 10.0
25 hypophosphatemia 10.0
26 hepatic veno-occlusive disease 10.0
27 osteomyelitis 10.0
28 osteomalacia 10.0
29 rickets 10.0
30 tethered spinal cord syndrome 10.0
31 respiratory failure 10.0
32 peripheral retinal degeneration 10.0
33 diarrhea 10.0
34 myelophthisic anemia 10.0
35 agammaglobulinemia 10.0
36 retinal degeneration 10.0
37 diencephalic syndrome 10.0
38 hypotonia 10.0
39 axial osteomalacia 9.8 TCIRG1 CLCN7
40 fibrogenesis imperfecta ossium 9.8 TCIRG1 CLCN7
41 brittle bone disorder 9.7 TNFSF11 CLCN7
42 beach ear 9.7 TCIRG1 CLCN7
43 osteopetrosis, autosomal recessive 3 9.7 TCIRG1 CLCN7
44 osteopetrosis, autosomal recessive 6 9.5 TNFSF11 TCIRG1 CLCN7
45 osteopetrosis, autosomal dominant 2 9.5 TNFSF11 TCIRG1 CLCN7
46 craniometaphyseal dysplasia, autosomal dominant 9.5 TNFSF11 TCIRG1 CLCN7
47 bone remodeling disease 9.5 TNFSF11 TCIRG1 CLCN7
48 osteopetrosis, autosomal recessive 8 9.5 TCIRG1 SNX10 CLCN7
49 osteochondrodysplasia 9.4 TNFSF11 TCIRG1 CLCN7
50 osteoporosis 9.4 TNFSF11 TCIRG1 CLCN7

Graphical network of the top 20 diseases related to Autosomal Recessive Malignant Osteopetrosis:



Diseases related to Autosomal Recessive Malignant Osteopetrosis

Symptoms & Phenotypes for Autosomal Recessive Malignant Osteopetrosis

Human phenotypes related to Autosomal Recessive Malignant Osteopetrosis:

58 30 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000256
2 nystagmus 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000639
3 tremor 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001337
4 hydrocephalus 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000238
5 hearing impairment 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000365
6 splenomegaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001744
7 hepatomegaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002240
8 bowing of the long bones 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0006487
9 recurrent respiratory infections 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002205
10 visual impairment 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000505
11 abnormality of visual evoked potentials 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000649
12 anemia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001903
13 reduced bone mineral density 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004349
14 growth delay 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001510
15 pallor 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000980
16 abnormality of temperature regulation 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004370
17 delayed eruption of teeth 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000684
18 recurrent fractures 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002757
19 otitis media 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000388
20 narrow chest 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000774
21 craniosynostosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001363
22 bone pain 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002653
23 abnormal blistering of the skin 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0008066
24 lymphadenopathy 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002716
25 optic nerve compression 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0007807
26 abnormality of hair texture 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0010719
27 osteopetrosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0011002
28 premature loss of primary teeth 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0006323
29 chronic rhinitis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002257
30 opsoclonus 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0010543
31 abnormal rib morphology 30 Hallmark (90%) HP:0000772
32 abnormal epiphysis morphology 30 Hallmark (90%) HP:0005930
33 abnormal metaphysis morphology 30 Hallmark (90%) HP:0000944
34 hypophosphatemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002148
35 cranial nerve paralysis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0006824
36 apnea 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002104
37 abnormal pulmonary valve morphology 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001641
38 hypocalcemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002901
39 bruising susceptibility 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000978
40 pulmonary arterial hypertension 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002092
41 pulmonary artery stenosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0004415
42 abnormality of the metaphysis 58 Very frequent (99-80%)
43 abnormality of movement 58 Very frequent (99-80%)
44 abnormality of the ribs 58 Very frequent (99-80%)
45 abnormality of epiphysis morphology 58 Very frequent (99-80%)
46 abnormality of metabolism/homeostasis 58 Very frequent (99-80%)

MGI Mouse Phenotypes related to Autosomal Recessive Malignant Osteopetrosis:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.46 CLCN7 SNX10 TCIRG1 TNFSF11
2 craniofacial MP:0005382 9.26 CLCN7 SNX10 TCIRG1 TNFSF11
3 skeleton MP:0005390 8.92 CLCN7 SNX10 TCIRG1 TNFSF11

Drugs & Therapeutics for Autosomal Recessive Malignant Osteopetrosis

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Levoleucovorin Approved, Experimental, Investigational Phase 1 68538-85-2, 58-05-9, 73951-54-9 149436 6006

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase I Clinical Trial for Gene Therapy in Infantile Malignant Osteopetrosis (IMO) to Evaluate the Safety and Preliminary Efficacy of Autologous CD34+ Enriched Cells Transduced With a LV Vector Encoding the TCIRG1 Gene Terminated NCT04525352 Phase 1

Search NIH Clinical Center for Autosomal Recessive Malignant Osteopetrosis

Genetic Tests for Autosomal Recessive Malignant Osteopetrosis

Anatomical Context for Autosomal Recessive Malignant Osteopetrosis

Organs/tissues related to Autosomal Recessive Malignant Osteopetrosis:

MalaCards : Bone, Eye, Skin, Bone Marrow, Brain

Publications for Autosomal Recessive Malignant Osteopetrosis

Articles related to Autosomal Recessive Malignant Osteopetrosis:

(show top 50) (show all 92)
# Title Authors PMID Year
1
Case report of mild TCIRG1-associated autosomal recessive osteopetrosis in Vietnam. 62
35915932 2022
2
Assessing the Efficacy of Alkylating Agent Regimens in the Treatment of Infantile Malignant Osteopetrosis: Cyclophosphamide, Busulfan, or Thiotepa. 62
35936184 2022
3
A Neonatal Case of Infantile Malignant Osteopetrosis Presenting with Thrombocytopenia and Hypotonicity: A Novel Mutation in Chloride Voltage-Gated Channel 7 Gene. 62
35515972 2022
4
Malignant infantile osteopetrosis in a 3-year-old Yemeni child: a case report. 62
36451718 2022
5
Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants. 62
34753502 2021
6
Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report. 62
34210262 2021
7
Managing challenging pain and irritability in OSTM1 mutation-related infantile malignant osteopetrosis. 62
34011644 2021
8
Gene therapy for infantile malignant osteopetrosis: review of pre-clinical research and proof-of-concept for phenotypic reversal. 62
33575431 2021
9
SNX10 gene mutation in infantile malignant osteopetrosis: A case report and literature review. 62
33678645 2021
10
Generation of gene-corrected functional osteoclasts from osteopetrotic induced pluripotent stem cells. 62
32414402 2020
11
V-ATPase a3 isoform mutations identified in osteopetrosis patients abolish its expression and disrupt osteoclast function. 62
32045577 2020
12
Malignant Infantile Osteopetrosis: A Case Report. 62
32015934 2020
13
Hematopoietic Stem Cell-Targeted Neonatal Gene Therapy with a Clinically Applicable Lentiviral Vector Corrects Osteopetrosis in oc/oc Mice. 62
31179768 2019
14
Targeting NSG Mice Engrafting Cells with a Clinically Applicable Lentiviral Vector Corrects Osteoclasts in Infantile Malignant Osteopetrosis. 62
28726516 2018
15
Whole exome sequencing identified two novel homozygous missense variants in the same codon of CLCN7 underlying autosomal recessive infantile malignant osteopetrosis in a Pakistani family. 62
29926385 2018
16
Successful hematopoietic stem cell transplantation for osteopetrosis using reduced intensity conditioning. 62
29469225 2018
17
Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis. 62
30539151 2018
18
[Identification of new mutations in TCIRG1 as a cause of infantile malignant osteopetrosis in two Mexican patients]. 62
29723947 2018
19
Novel mutations of TCIRG1 cause a malignant and mild phenotype of autosomal recessive osteopetrosis (ARO) in four Chinese families. 62
28816234 2017
20
Coexisting variants in OSTM1 and MANEAL cause a complex neurodegenerative disorder with NBIA-like brain abnormalities. 62
28612835 2017
21
[Analysis of TCIRG1 gene mutation in a Chinese family affected with infantile malignant osteopetrosis]. 62
28604959 2017
22
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy. 62
27541021 2016
23
Extending the Spectrum of Radiological Findings in Patients With Severe Osteopetrosis and Different Genetic Backgrounds. 62
26970326 2016
24
Identification and Characterization of Mutations in the CLCN7 Gene in a Taiwanese Patient with Infantile Malignant Osteopetrosis. 62
26365571 2016
25
Improved Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Infantile Malignant Osteopetrosis Using Fludarabine-Based Conditioning. 62
26485304 2016
26
A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient. 62
26477479 2016
27
Unmistakable Morphology? Infantile Malignant Osteopetrosis Resembling Juvenile Myelomonocytic Leukemia in Infants. 62
25982139 2015
28
[Preimplantation genetic diagnosis of infantile malignant osteopetrosis in a Chinese family]. 62
26037338 2015
29
A fatal case of infantile malignant osteopetrosis complicated by pulmonary arterial hypertension after hematopoietic stem cell transplantation. 62
25504019 2014
30
Osteopetrosis mimicking juvenile myelomonocytic leukemia. 62
25335998 2014
31
Identification of novel mutation in autosomal recessive infantile malignant osteopetrosis. 62
24101165 2014
32
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis. 62
23907031 2013
33
Infantile malignant osteopetrosis. 62
23721911 2013
34
Severe neuronopathic autosomal recessive osteopetrosis due to homozygous deletions affecting OSTM1. 62
23685543 2013
35
Osteopetrosis mutation R444L causes endoplasmic reticulum retention and misprocessing of vacuolar H+-ATPase a3 subunit. 62
22685294 2012
36
Infantile malignant osteopetrosis: report of 2 cases with osteomyelitis of the jaws. 62
22828766 2012
37
Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis. 62
22044152 2012
38
Infantile malignant osteopetrosis: a rare cause of neonatal hypocalcemia. 62
23329773 2012
39
[Bilateral optic nerve decompression at infantile-malignant osteopetrosis and Silver-Russell-syndrome]. 62
21437846 2011
40
Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients. 62
21042819 2011
41
Scarcity despite wealth: osteopetrorickets. 62
21175093 2010
42
Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low-level engraftment and lack of selective expansion of the osteoclastic lineage. 62
20568230 2010
43
[Genetic basis for skeletal disease. Molecular advances in sclerosing bone disorders]. 62
20675930 2010
44
Osteopetrorickets: infantile malignant osteopetrosis paradoxically complicated by rickets. 62
19756570 2010
45
Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis. 62
20424301 2010
46
A single-center experience in 20 patients with infantile malignant osteopetrosis. 62
19507210 2009
47
Prospects for gene therapy of osteopetrosis. 62
19519360 2009
48
Osteomyelitis of the mandible secondary to infantile osteopetrosis: a case report. 62
19464639 2009
49
Low-dose busulphan conditioning and neonatal stem cell transplantation preserves vision and restores hematopoiesis in severe murine osteopetrosis. 62
19100677 2009
50
Rare gross deletion in T-cell immune regulator-1 gene in Iranian family with infantile malignant osteopetrosis. 62
18946580 2008

Variations for Autosomal Recessive Malignant Osteopetrosis

Expression for Autosomal Recessive Malignant Osteopetrosis

Search GEO for disease gene expression data for Autosomal Recessive Malignant Osteopetrosis.

Pathways for Autosomal Recessive Malignant Osteopetrosis

Pathways related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.43 TCIRG1 CLCN7
2 9.97 TNFSF11 TCIRG1 SNX10 CLCN7

GO Terms for Autosomal Recessive Malignant Osteopetrosis

Biological processes related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to leukemia inhibitory factor GO:1990830 9.71 TNFSF11 SNX10
2 ossification GO:0001503 9.67 TNFSF11 TCIRG1
3 osteoclast differentiation GO:0030316 9.63 TNFSF11 TCIRG1 SNX10
4 calcium ion homeostasis GO:0055074 9.62 TNFSF11 SNX10
5 osteoclast proliferation GO:0002158 9.56 TNFSF11 TCIRG1
6 bone resorption GO:0045453 9.43 TNFSF11 TCIRG1 SNX10
7 tooth eruption GO:0044691 9.1 TNFSF11 TCIRG1 SNX10

Molecular functions related to Autosomal Recessive Malignant Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 8.92 TCIRG1 SNX10

Sources for Autosomal Recessive Malignant Osteopetrosis

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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