MCID: OST126
MIFTS: 36

Osteopetrosis, Autosomal Recessive 1

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

Aliases & Classifications for Osteopetrosis, Autosomal Recessive 1

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 1:

Name: Osteopetrosis, Autosomal Recessive 1 57 75 13 73
Optb1 57 12 53 75
Osteopetrosis Autosomal Recessive 1 53 29 6
Autosomal Recessive Albers-Schonberg Disease 12 75
Infantile Malignant Osteopetrosis 75 73
Albers-Schonberg Disease, Autosomal Recessive 57
Osteopetrosis, Autosomal Recessive, Type 1 40
Autosomal Recessive Osteopetrosis Type 1 53
Osteopetrosis, Infantile Malignant 1 57
Autosomal Recessive Osteopetrosis 1 12
Infantile Malignant Osteopetrosis 1 12
Osteopetrosis Infantile Malignant 1 53
Marble Bones, Autosomal Recessive 57
Marble Bones Autosomal Recessive 53

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity (see )


HPO:

32
osteopetrosis, autosomal recessive 1:
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Osteopetrosis, Autosomal Recessive 1

OMIM : 57 Osteopetrosis (OPT) is a life-threatening disease caused by subnormal osteoclast function, with an incidence of 1 in 250,000 births. The disease usually manifests in the first few months of life with macrocephaly and frontal bossing, resulting in a characteristic facial appearance. Defective bone remodeling of the skull results in choanal stenosis with concomitant respiratory problems and feeding difficulties, which are the first clinical manifestation of disease. The expanding bone encroaches on neural foramina, leading to blindness, deafness, and facial palsy. Complete visual loss invariably occurs in all untreated patients, and hearing loss is estimated to affect 78% of patients with OPT. Tooth eruption defects and severe dental caries are common. Calcium feedback hemostasis is impaired, and children with OPT are at risk of developing hypocalcemia with attendant tetanic seizures and secondary hyperparathyroidism. The most severe complication of OPT, limiting survival, is bone marrow insufficiency. The abnormal expansion of cortical and trabecular bone physically limits the availability of medullary space for hematopoietic activity, leading to life-threatening cytopenia and secondary expansion of extramedullary hematopoiesis at sites such as the liver and spleen (summary by Aker et al., 2012). (259700)

MalaCards based summary : Osteopetrosis, Autosomal Recessive 1, also known as optb1, is related to autosomal recessive malignant osteopetrosis and osteopetrosis, autosomal recessive 5, and has symptoms including ophthalmoplegia An important gene associated with Osteopetrosis, Autosomal Recessive 1 is TCIRG1 (T Cell Immune Regulator 1, ATPase H+ Transporting V0 Subunit A3). Affiliated tissues include bone, bone marrow and liver, and related phenotypes are hydrocephalus and macrocephaly

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous or compound heterozygous mutation in the TCIRG1 gene on chromosome 11q13.2.

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.

UniProtKB/Swiss-Prot : 75 Osteopetrosis, autosomal recessive 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. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.

Related Diseases for Osteopetrosis, Autosomal Recessive 1

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



Diseases related to Osteopetrosis, Autosomal Recessive 1

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 1

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly

Neurologic Central Nervous System:
hydrocephalus
cranial nerve palsies
seizures (tetany)

Growth Weight:
failure to thrive

Abdomen Liver:
hepatomegaly

Skeletal:
osteomyelitis
pathologic fractures
uniformly dense skeleton
bone-within-bone appearance

Laboratory Abnormalities:
elevated alkaline phosphatase
low serum calcium
elevated serum phosphorus

Head And Neck Teeth:
dental caries
distorted primary molars

Skeletal Spine:
sandwich appearance of vertebral bodies

Head And Neck Face:
frontal bossing
facial paralysis

Head And Neck Eyes:
nystagmus
optic atrophy
blindness
extraocular muscle paralysis

AbdomenSpleen:
splenomegaly

Hematology:
anemia
pancytopenia

Skeletal Pelvis:
coxa vara

Head And Neck Ears:
deafness

Skeletal Skull:
thick, dense skull
narrowness of neural and vascular foramina

Skeletal Limbs:
splayed metaphyses


Clinical features from OMIM:

259700

Human phenotypes related to Osteopetrosis, Autosomal Recessive 1:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 hydrocephalus 32 HP:0000238
2 macrocephaly 32 HP:0000256
3 hearing impairment 32 HP:0000365
4 ophthalmoparesis 32 HP:0000597
5 blindness 32 HP:0000618
6 nystagmus 32 HP:0000639
7 optic atrophy 32 HP:0000648
8 carious teeth 32 HP:0000670
9 seizures 32 HP:0001250
10 tetany 32 HP:0001281
11 failure to thrive 32 HP:0001508
12 splenomegaly 32 HP:0001744
13 pancytopenia 32 HP:0001876
14 anemia 32 HP:0001903
15 frontal bossing 32 HP:0002007
16 hepatomegaly 32 HP:0002240
17 osteomyelitis 32 HP:0002754
18 pathologic fracture 32 HP:0002756
19 coxa vara 32 HP:0002812
20 flared metaphysis 32 HP:0003015
21 elevated alkaline phosphatase 32 HP:0003155
22 sandwich appearance of vertebral bodies 32 HP:0004618
23 facial paralysis 32 HP:0007209
24 facial palsy 32 HP:0010628
25 osteopetrosis 32 HP:0011002

UMLS symptoms related to Osteopetrosis, Autosomal Recessive 1:


ophthalmoplegia

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 1

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

Genetic Tests for Osteopetrosis, Autosomal Recessive 1

Genetic tests related to Osteopetrosis, Autosomal Recessive 1:

# Genetic test Affiliating Genes
1 Osteopetrosis Autosomal Recessive 1 29 TCIRG1

Anatomical Context for Osteopetrosis, Autosomal Recessive 1

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

41
Bone, Bone Marrow, Liver, Spleen, T Cells

Publications for Osteopetrosis, Autosomal Recessive 1

Articles related to Osteopetrosis, Autosomal Recessive 1:

(show all 27)
# Title Authors Year
1
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. ( 29926385 )
2018
2
Targeting NSG Mice Engrafting Cells with a Clinically Applicable Lentiviral Vector Corrects Osteoclasts in Infantile Malignant Osteopetrosis. ( 28726516 )
2017
3
[Analysis of TCIRG1 gene mutation in a Chinese family affected with infantile malignant osteopetrosis]. ( 28604959 )
2017
4
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy. ( 27541021 )
2016
5
Improved Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Infantile Malignant Osteopetrosis Using Fludarabine-Based Conditioning. ( 26485304 )
2015
6
Identification and Characterization of Mutations in the CLCN7 Gene in a Taiwanese Patient with Infantile Malignant Osteopetrosis. ( 26365571 )
2015
7
A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient. ( 26477479 )
2015
8
Diagnosis: Infantile Malign Osteopetrosis. ( 25330538 )
2014
9
A fatal case of infantile malignant osteopetrosis complicated by pulmonary arterial hypertension after hematopoietic stem cell transplantation. ( 25504019 )
2014
10
Identification of Novel Mutation in Autosomal Recessive Infantile Malignant Osteopetrosis. ( 24101165 )
2013
11
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis. ( 23907031 )
2013
12
Infantile malignant osteopetrosis. ( 23721911 )
2013
13
Infantile malignant osteopetrosis: a rare cause of neonatal hypocalcemia. ( 23329773 )
2012
14
Infantile malignant osteopetrosis: report of 2 cases with osteomyelitis of the jaws. ( 22828766 )
2012
15
Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients. ( 21042819 )
2011
16
Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis. ( 20424301 )
2010
17
Osteopetrorickets: infantile malignant osteopetrosis paradoxically complicated by rickets. ( 19756570 )
2010
18
A single-center experience in 20 patients with infantile malignant osteopetrosis. ( 19507210 )
2009
19
Rare gross deletion in T-cell immune regulator-1 gene in Iranian family with infantile malignant osteopetrosis. ( 18946580 )
2008
20
Chloride channel CICN7 mutations in a Korean patient with infantile malignant osteopetrosis initially presenting with neonatal thrombocytopenia. ( 15116126 )
2004
21
Hematological defects in the oc/oc mouse, a model of infantile malignant osteopetrosis. ( 15284856 )
2004
22
Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis. ( 12552563 )
2003
23
Novel mutations in the a3 subunit of vacuolar H(+)-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis. ( 11856654 )
2002
24
Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. ( 10942435 )
2000
25
Distal phalangeal resorption in an adult with infantile malignant osteopetrosis: a case report. ( 9523972 )
1998
26
Bone marrow transplantation for infantile malignant osteopetrosis. ( 7583393 )
1995
27
Infantile malignant osteopetrosis presenting as bilateral choanal atresia: Report of two cases. ( 17588000 )
1993

Variations for Osteopetrosis, Autosomal Recessive 1

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

75
# Symbol AA change Variation ID SNP ID
1 TCIRG1 p.Gly405Arg VAR_019569 rs137853150
2 TCIRG1 p.Arg444Leu VAR_019570 rs137853151
3 TCIRG1 p.Ala141Pro VAR_020988
4 TCIRG1 p.Asp517Asn VAR_020990 rs369264588
5 TCIRG1 p.Pro775Arg VAR_020991

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 1:

6
(show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 TCIRG1 TCIRG1, 1-BP DEL, 5272C deletion Pathogenic
2 TCIRG1 NM_006019.3(TCIRG1): c.1392C> A (p.Cys464Ter) single nucleotide variant Pathogenic rs137853149 GRCh37 Chromosome 11, 67815200: 67815200
3 TCIRG1 NM_006019.3(TCIRG1): c.1392C> A (p.Cys464Ter) single nucleotide variant Pathogenic rs137853149 GRCh38 Chromosome 11, 68047733: 68047733
4 TCIRG1 TCIRG1,IVS15AS, G-A, -1 single nucleotide variant Pathogenic
5 TCIRG1 TCIRG1, IVS2AS, A-T, +4 single nucleotide variant Pathogenic
6 TCIRG1 NM_006019.3(TCIRG1): c.1213G> A (p.Gly405Arg) single nucleotide variant Pathogenic rs137853150 GRCh37 Chromosome 11, 67814947: 67814947
7 TCIRG1 NM_006019.3(TCIRG1): c.1213G> A (p.Gly405Arg) single nucleotide variant Pathogenic rs137853150 GRCh38 Chromosome 11, 68047480: 68047480
8 TCIRG1 NM_006019.3(TCIRG1): c.1331G> T (p.Arg444Leu) single nucleotide variant Pathogenic rs137853151 GRCh37 Chromosome 11, 67815139: 67815139
9 TCIRG1 NM_006019.3(TCIRG1): c.1331G> T (p.Arg444Leu) single nucleotide variant Pathogenic rs137853151 GRCh38 Chromosome 11, 68047672: 68047672
10 TCIRG1 TCIRG1, 26-BP DEL, CODON 216 deletion Pathogenic
11 TCIRG1 NM_006019.3(TCIRG1): c.1674-1G> A single nucleotide variant Pathogenic rs139617644 GRCh37 Chromosome 11, 67816547: 67816547
12 TCIRG1 NM_006019.3(TCIRG1): c.1674-1G> A single nucleotide variant Pathogenic rs139617644 GRCh38 Chromosome 11, 68049080: 68049080
13 TCIRG1 NM_006019.3(TCIRG1): c.1249G> A (p.Ala417Thr) single nucleotide variant Uncertain significance rs140963213 GRCh37 Chromosome 11, 67814983: 67814983
14 TCIRG1 NM_006019.3(TCIRG1): c.1249G> A (p.Ala417Thr) single nucleotide variant Uncertain significance rs140963213 GRCh38 Chromosome 11, 68047516: 68047516
15 TCIRG1 NM_006019.3(TCIRG1): c.1800C> T (p.Ala600=) single nucleotide variant Conflicting interpretations of pathogenicity rs145144233 GRCh37 Chromosome 11, 67816674: 67816674
16 TCIRG1 NM_006019.3(TCIRG1): c.1800C> T (p.Ala600=) single nucleotide variant Conflicting interpretations of pathogenicity rs145144233 GRCh38 Chromosome 11, 68049207: 68049207
17 TCIRG1 NM_006019.3(TCIRG1): c.1559G> A (p.Trp520Ter) single nucleotide variant Likely pathogenic rs1057517365 GRCh38 Chromosome 11, 68048883: 68048883
18 TCIRG1 NM_006019.3(TCIRG1): c.1559G> A (p.Trp520Ter) single nucleotide variant Likely pathogenic rs1057517365 GRCh37 Chromosome 11, 67816350: 67816350
19 TCIRG1 NM_006019.3(TCIRG1): c.703delAinsAA (p.Ile235Asnfs) indel Pathogenic GRCh37 Chromosome 11, 67811110: 67811110
20 TCIRG1 NM_006019.3(TCIRG1): c.703delAinsAA (p.Ile235Asnfs) indel Pathogenic GRCh38 Chromosome 11, 68043643: 68043643
21 TCIRG1 NM_006019.3(TCIRG1): c.292C> T (p.Gln98Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 11, 67810205: 67810205
22 TCIRG1 NM_006019.3(TCIRG1): c.292C> T (p.Gln98Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 11, 68042738: 68042738

Expression for Osteopetrosis, Autosomal Recessive 1

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

Pathways for Osteopetrosis, Autosomal Recessive 1

GO Terms for Osteopetrosis, Autosomal Recessive 1

Sources for Osteopetrosis, Autosomal Recessive 1

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