OI15
MCID: OST110
MIFTS: 38

Osteogenesis Imperfecta, Type Xv (OI15)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Oral diseases, Rare diseases

Aliases & Classifications for Osteogenesis Imperfecta, Type Xv

MalaCards integrated aliases for Osteogenesis Imperfecta, Type Xv:

Name: Osteogenesis Imperfecta, Type Xv 56 29 13 6 39 71
Oi15 56 12 73
Osteogenesis Imperfecta Type 15 12 15
Osteogenesis Imperfecta Type Xv 12 73
Osteogenesis Imperfecta 15 73
Oi, Type Xv 56
Oi Type Xv 73
Oi-Xv 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
osteogenesis imperfecta, type xv:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110347
OMIM 56 615220
OMIM Phenotypic Series 56 PS166200
MeSH 43 D010013
ICD10 32 Q78.0
UMLS 71 C3808844

Summaries for Osteogenesis Imperfecta, Type Xv

OMIM : 56 Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Keupp et al. (2013) and Pyott et al. (2013) described osteogenesis imperfecta type XV, an autosomal recessive form of the disorder characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclera. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients. (615220)

MalaCards based summary : Osteogenesis Imperfecta, Type Xv, also known as oi15, is related to osteoporosis-pseudoglioma syndrome and osteogenesis imperfecta, type xvi. An important gene associated with Osteogenesis Imperfecta, Type Xv is WNT1 (Wnt Family Member 1), and among its related pathways/superpathways are DNA Damage Response (only ATM dependent) and WNT ligand biogenesis and trafficking. Affiliated tissues include bone, brain and hypothalamus, and related phenotypes are global developmental delay and joint hypermobility

Disease Ontology : 12 An osteogenesis imperfecta that has material basis in mutation in the WNT1 gene on chromosome 12q13.

UniProtKB/Swiss-Prot : 73 Osteogenesis imperfecta 15: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI15 is characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclerae. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients.

Related Diseases for Osteogenesis Imperfecta, Type Xv

Graphical network of the top 20 diseases related to Osteogenesis Imperfecta, Type Xv:



Diseases related to Osteogenesis Imperfecta, Type Xv

Symptoms & Phenotypes for Osteogenesis Imperfecta, Type Xv

Human phenotypes related to Osteogenesis Imperfecta, Type Xv:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 very rare (1%) HP:0001263
2 joint hypermobility 31 very rare (1%) HP:0001382
3 recurrent fractures 31 very rare (1%) HP:0002757
4 blue sclerae 31 very rare (1%) HP:0000592
5 bowing of limbs due to multiple fractures 31 very rare (1%) HP:0003023
6 scoliosis 31 HP:0002650
7 short stature 31 HP:0004322
8 platyspondyly 31 HP:0000926
9 cerebellar hypoplasia 31 HP:0001321
10 thin ribs 31 HP:0000883
11 hypoplasia of the pons 31 HP:0012110
12 schizencephaly 31 HP:0010636

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis
platyspondyly
vertebral fractures

Chest Ribs Sternum Clavicles And Scapulae:
thin ribs

Skeletal:
low bone density
lack of bone modeling

Skeletal Limbs:
bowing of lower extremities
bowing of upper extremities
shortening of upper extremities
shortening of lower extremities
multiple fractures of extremities
more
Growth Height:
short stature

Neurologic Central Nervous System:
developmental delay
pontine hypoplasia
brain malformation
unilateral cerebellar hypoplasia
congenital absence of the vermis
more
Head And Neck Eyes:
blue sclera

Skeletal Skull:
diminished calvarial mineralization

Clinical features from OMIM:

615220

Drugs & Therapeutics for Osteogenesis Imperfecta, Type Xv

Search Clinical Trials , NIH Clinical Center for Osteogenesis Imperfecta, Type Xv

Genetic Tests for Osteogenesis Imperfecta, Type Xv

Genetic tests related to Osteogenesis Imperfecta, Type Xv:

# Genetic test Affiliating Genes
1 Osteogenesis Imperfecta, Type Xv 29 WNT1

Anatomical Context for Osteogenesis Imperfecta, Type Xv

MalaCards organs/tissues related to Osteogenesis Imperfecta, Type Xv:

40
Bone, Brain, Hypothalamus, Pons, Cerebellum

Publications for Osteogenesis Imperfecta, Type Xv

Articles related to Osteogenesis Imperfecta, Type Xv:

(show all 24)
# Title Authors PMID Year
1
Mutations in WNT1 are a cause of osteogenesis imperfecta. 6 56
23434763 2013
2
Mutations in WNT1 cause different forms of bone fragility. 6 56
23499309 2013
3
WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta. 6 56
23499310 2013
4
Variable brain phenotype primarily affects the brainstem and cerebellum in patients with osteogenesis imperfecta caused by recessive WNT1 mutations. 56
26671912 2016
5
The swaying mouse as a model of osteogenesis imperfecta caused by WNT1 mutations. 56
24634143 2014
6
WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. 56
23656646 2013
7
Audiometric, surgical, and genetic findings in 15 ears of patients with osteogenesis imperfecta. 6
19358256 2009
8
Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships. 6
18996919 2009
9
Evidence that abnormal high bone mineralization in growing children with osteogenesis imperfecta is not associated with specific collagen mutations. 6
18311573 2008
10
Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. 6
17078022 2007
11
Osteogenesis imperfecta: clinical, biochemical and molecular findings. 6
16879195 2006
12
COL1A1/2 Osteogenesis Imperfecta 6
20301472 2005
13
Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing loss in osteogenesis imperfecta patients. 6
15241796 2004
14
Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients. 6
15024745 2004
15
Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV. 6
11317364 2001
16
Prenatal diagnosis of a novel COL1A1 mutation in osteogenesis imperfecta type I carried through full term pregnancy. 6
11113887 2000
17
Substitution of arginine for glycine at position 154 of the alpha 1 chain of type I collagen in a variant of osteogenesis imperfecta: comparison to previous cases with the same mutation. 6
8669434 1996
18
Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen. 6
7942841 1994
19
Swaying is a mutant allele of the proto-oncogene Wnt-1. 56
1835670 1991
20
Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen. 6
2037280 1991
21
The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the triple-helical domain of pro-alpha 1(I) chains. 6
3722186 1986
22
Genetic heterogeneity in osteogenesis imperfecta. 56
458828 1979
23
Successful aortic valve replacement for aortic regurgitation associated with osteogenesis imperfecta. 6
1137656 1975
24
Mice Carrying a Ubiquitous R235W Mutation of Wnt1 Display a Bone-Specific Phenotype. 61
32369212 2020

Variations for Osteogenesis Imperfecta, Type Xv

ClinVar genetic disease variations for Osteogenesis Imperfecta, Type Xv:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WNT1 NM_005430.4(WNT1):c.859dup (p.His287fs)duplication Pathogenic,risk factor 50257 rs387907353 12:49375163-49375164 12:48981380-48981381
2 WNT1 NM_005430.4(WNT1):c.624+4A>GSNV Pathogenic 50258 rs387907354 12:49374476-49374476 12:48980693-48980693
3 WNT1 NM_005430.4(WNT1):c.565G>T (p.Glu189Ter)SNV Pathogenic 50259 rs387907355 12:49374413-49374413 12:48980630-48980630
4 WNT1 NM_005430.4(WNT1):c.884C>A (p.Ser295Ter)SNV Pathogenic 50260 rs387907356 12:49375194-49375194 12:48981411-48981411
5 WNT1 NM_005430.4(WNT1):c.946_949dup (p.Ser317fs)duplication Pathogenic 50261 rs387907357 12:49375255-49375256 12:48981472-48981473
6 WNT1 NM_005430.4(WNT1):c.1026del (p.Glu343fs)deletion Pathogenic 180210 rs727505392 12:49375335-49375335 12:48981552-48981552
7 WNT1 NM_005430.4(WNT1):c.104+4_104+44deldeletion Likely pathogenic 488347 rs1555178899 12:49372540-49372580 12:48978757-48978797
8 WNT1 NM_005430.4(WNT1):c.1063G>T (p.Val355Phe)SNV Conflicting interpretations of pathogenicity 50262 rs387907358 12:49375373-49375373 12:48981590-48981590
9 WNT1 NM_005430.4(WNT1):c.1090C>G (p.Arg364Gly)SNV Uncertain significance 592130 rs1435433748 12:49375400-49375400 12:48981617-48981617
10 WNT1 NM_005430.4(WNT1):c.1060del (p.His354fs)deletion Uncertain significance 873444 12:49375369-49375369 12:48981586-48981586

UniProtKB/Swiss-Prot genetic disease variations for Osteogenesis Imperfecta, Type Xv:

73
# Symbol AA change Variation ID SNP ID
1 WNT1 p.Cys143Phe VAR_069627
2 WNT1 p.Gly177Cys VAR_069628
3 WNT1 p.Phe298Cys VAR_069631
4 WNT1 p.Val355Phe VAR_069632 rs387907358
5 WNT1 p.Glu123Asp VAR_079407
6 WNT1 p.Cys153Gly VAR_079408

Expression for Osteogenesis Imperfecta, Type Xv

Search GEO for disease gene expression data for Osteogenesis Imperfecta, Type Xv.

Pathways for Osteogenesis Imperfecta, Type Xv

Pathways related to Osteogenesis Imperfecta, Type Xv according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.02 WNT10B WNT1
2
Show member pathways
10.36 WNT10B WNT1

GO Terms for Osteogenesis Imperfecta, Type Xv

Biological processes related to Osteogenesis Imperfecta, Type Xv according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of DNA-binding transcription factor activity GO:0051091 9.32 WNT10B WNT1
2 canonical Wnt signaling pathway GO:0060070 9.26 WNT10B WNT1
3 cell fate commitment GO:0045165 9.16 WNT10B WNT1
4 negative regulation of fat cell differentiation GO:0045599 8.96 WNT10B WNT1
5 hematopoietic stem cell proliferation GO:0071425 8.62 WNT10B WNT1

Molecular functions related to Osteogenesis Imperfecta, Type Xv according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 frizzled binding GO:0005109 8.96 WNT10B WNT1
2 receptor ligand activity GO:0048018 8.62 WNT10B WNT1

Sources for Osteogenesis Imperfecta, Type Xv

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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