BRKS2
MCID: BRC048
MIFTS: 32

Bruck Syndrome 2 (BRKS2)

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

Aliases & Classifications for Bruck Syndrome 2

MalaCards integrated aliases for Bruck Syndrome 2:

Name: Bruck Syndrome 2 57 20 72 29 13 6 70
Osteogenesis Imperfecta with Congenital Joint Contractures 57 72 6
Brks2 57 20 72
Syndrome, Bruck, Type 2 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
bruck syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Bruck Syndrome 2

UniProtKB/Swiss-Prot : 72 Bruck syndrome 2: An autosomal recessive disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia. It is distinguished from osteogenesis imperfecta by the absence of hearing loss and dentinogenesis imperfecta, and by the presence of clubfoot and congenital joint limitations.

MalaCards based summary : Bruck Syndrome 2, also known as osteogenesis imperfecta with congenital joint contractures, is related to dentinogenesis imperfecta and bruck syndrome. An important gene associated with Bruck Syndrome 2 is PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2). Affiliated tissues include bone, and related phenotypes are osteopenia and inguinal hernia

More information from OMIM: 609220

Related Diseases for Bruck Syndrome 2

Diseases in the Bruck Syndrome family:

Bruck Syndrome 1 Bruck Syndrome 2

Diseases related to Bruck Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)
# Related Disease Score Top Affiliating Genes
1 dentinogenesis imperfecta 30.2 PLOD2 FKBP10
2 bruck syndrome 29.6 PLOD2 FKBP10
3 brittle bone disorder 29.5 PLOD2 FKBP10
4 scoliosis 29.2 PLOD2 FKBP10
5 bruck syndrome 1 11.1
6 torticollis 10.3
7 congenital amyoplasia 10.3
8 cleft soft palate 10.0
9 protrusio acetabuli 10.0
10 velocardiofacial syndrome 10.0
11 congenital contractures 10.0
12 osteogenesis imperfecta, type iii 9.7 PLOD2 FKBP10
13 multiple pterygium syndrome, escobar variant 9.7 PLOD2 FKBP10
14 odontochondrodysplasia 9.6 PLOD2 FKBP10

Graphical network of the top 20 diseases related to Bruck Syndrome 2:



Diseases related to Bruck Syndrome 2

Symptoms & Phenotypes for Bruck Syndrome 2

Human phenotypes related to Bruck Syndrome 2:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 osteopenia 31 HP:0000938
2 inguinal hernia 31 HP:0000023
3 pectus carinatum 31 HP:0000768
4 short stature 31 HP:0004322
5 flexion contracture 31 HP:0001371
6 elbow flexion contracture 31 HP:0002987
7 talipes equinovarus 31 HP:0001762
8 platyspondyly 31 HP:0000926
9 wormian bones 31 HP:0002645
10 pterygium 31 HP:0001059
11 knee flexion contracture 31 HP:0006380
12 femoral bowing 31 HP:0002980
13 increased susceptibility to fractures 31 HP:0002659
14 hydroxyprolinuria 31 HP:0003080

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal:
osteopenia
bone fragility
congenital joint contracture (elbow and knees)

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum

Skeletal Skull:
wormian bones

Skeletal Feet:
clubfeet

Skin Nails Hair Skin:
pterygia

Genitourinary External Genitalia Male:
inguinal hernia

Growth Height:
short stature

Skeletal Limbs:
femoral bowing

Laboratory Abnormalities:
elevated urinary hydroxyproline

Skeletal Spine:
platyspondyly (thoracic vertebrae)

Clinical features from OMIM®:

609220 (Updated 05-Apr-2021)

Drugs & Therapeutics for Bruck Syndrome 2

Search Clinical Trials , NIH Clinical Center for Bruck Syndrome 2

Genetic Tests for Bruck Syndrome 2

Genetic tests related to Bruck Syndrome 2:

# Genetic test Affiliating Genes
1 Bruck Syndrome 2 29 PLOD2

Anatomical Context for Bruck Syndrome 2

MalaCards organs/tissues related to Bruck Syndrome 2:

40
Bone

Publications for Bruck Syndrome 2

Articles related to Bruck Syndrome 2:

(show all 16)
# Title Authors PMID Year
1
Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome--osteogenesis imperfecta phenotypic spectrum. 57 6
22689593 2012
2
Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2. 57 6
15523624 2004
3
Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis. 57 6
12881513 2003
4
Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17. 6 57
9927692 1999
5
Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations. 6
23712425 2013
6
Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. 6
22949511 2013
7
Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. 6
22718341 2012
8
Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans. 6
21567934 2011
9
Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. 6
20839288 2011
10
FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification? 6
20696291 2010
11
Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. 6
20362275 2010
12
Bruck syndrome: a rare combination of bone fragility and multiple congenital joint contractures. 6
9481655 1998
13
Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): review and report on the first North American case. 6
9129737 1997
14
Case Report: Exome Sequencing Identified a Novel Compound Heterozygous Variation in PLOD2 Causing Bruck Syndrome Type 2. 61
33664768 2021
15
Bruck syndrome 2 variant lacking congenital contractures and involving a novel compound heterozygous PLOD2 mutation. 61
31472299 2020
16
Expanding the Clinical Spectrum of Phenotypes Caused by Pathogenic Variants in PLOD2. 61
29178448 2018

Variations for Bruck Syndrome 2

ClinVar genetic disease variations for Bruck Syndrome 2:

6 (show top 50) (show all 95)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PLOD2 NM_182943.3(PLOD2):c.1886C>T (p.Thr629Ile) SNV Pathogenic 7641 rs121434459 GRCh37: 3:145789173-145789173
GRCh38: 3:146071386-146071386
2 PLOD2 NM_182943.3(PLOD2):c.1865G>T (p.Gly622Val) SNV Pathogenic 7642 rs121434460 GRCh37: 3:145789194-145789194
GRCh38: 3:146071407-146071407
3 PLOD2 NM_182943.3(PLOD2):c.1856G>A (p.Arg619His) SNV Pathogenic 7643 rs121434461 GRCh37: 3:145789203-145789203
GRCh38: 3:146071416-146071416
4 FKBP10 FKBP10, 8-BP DUP, NT1016 Duplication Pathogenic 30631 GRCh37:
GRCh38:
5 FKBP10 NM_021939.3(FKBP10):c.1276dup (p.Gln426fs) Duplication Pathogenic 30633 rs1567856056 GRCh37: 17:39977212-39977213
GRCh38: 17:41820960-41820961
6 FKBP10 NM_021939.3(FKBP10):c.344G>A (p.Arg115Gln) SNV Pathogenic 30634 rs387906960 GRCh37: 17:39973408-39973408
GRCh38: 17:41817156-41817156
7 FKBP10 NM_021939.3(FKBP10):c.743dup (p.Gln249fs) Duplication Pathogenic 30635 rs1555616552 GRCh37: 17:39975471-39975472
GRCh38: 17:41819219-41819220
8 PLOD2 NM_182943.3(PLOD2):c.1559dup (p.Val523fs) Duplication Pathogenic 41424 rs749709000 GRCh37: 3:145795652-145795653
GRCh38: 3:146077865-146077866
9 FKBP10 NM_021939.3(FKBP10):c.1271_1272delinsA (p.Ala424fs) Indel Pathogenic 41425 rs397509383 GRCh37: 17:39977213-39977214
GRCh38: 17:41820961-41820962
10 FKBP10 NM_021939.3(FKBP10):c.831dup (p.Gly278fs) Duplication Pathogenic 438659 rs137853883 GRCh37: 17:39975558-39975559
GRCh38: 17:41819306-41819307
11 FKBP10 NM_021939.3(FKBP10):c.337G>A (p.Glu113Lys) SNV Pathogenic 41473 rs397514674 GRCh37: 17:39973401-39973401
GRCh38: 17:41817149-41817149
12 FKBP10 NM_021939.3(FKBP10):c.877_879del (p.Tyr293del) Deletion Pathogenic 208427 rs869320752 GRCh37: 17:39975609-39975611
GRCh38: 17:41819357-41819359
13 FKBP10 NM_021939.4(FKBP10):c.921C>G (p.Tyr307Ter) SNV Pathogenic 1028229 GRCh37: 17:39975785-39975785
GRCh38: 17:41819533-41819533
14 PLOD2 NM_182943.3(PLOD2):c.1280A>G (p.Asn427Ser) SNV Likely pathogenic 807467 rs893004444 GRCh37: 3:145799603-145799603
GRCh38: 3:146081816-146081816
15 PLOD2 NM_182943.3(PLOD2):c.351dup (p.Phe118fs) Duplication Likely pathogenic 930725 GRCh37: 3:145828222-145828223
GRCh38: 3:146110435-146110436
16 FKBP10 NM_021939.3(FKBP10):c.890_897dup (p.Gly300Ter) Duplication Likely pathogenic 631496 rs1567855132 GRCh37: 17:39975623-39975624
GRCh38: 17:41819371-41819372
17 PLOD2 NM_182943.3(PLOD2):c.2110G>A (p.Glu704Lys) SNV Uncertain significance 900155 GRCh37: 3:145788840-145788840
GRCh38: 3:146071053-146071053
18 PLOD2 NM_182943.3(PLOD2):c.1658A>G (p.Gln553Arg) SNV Uncertain significance 343646 rs148051196 GRCh37: 3:145794588-145794588
GRCh38: 3:146076801-146076801
19 PLOD2 NM_182943.3(PLOD2):c.382A>G (p.Lys128Glu) SNV Uncertain significance 343651 rs200569129 GRCh37: 3:145828192-145828192
GRCh38: 3:146110405-146110405
20 PLOD2 NM_182943.3(PLOD2):c.-73C>T SNV Uncertain significance 343653 rs148948195 GRCh37: 3:145878849-145878849
GRCh38: 3:146161062-146161062
21 PLOD2 NM_182943.3(PLOD2):c.801C>A (p.Asn267Lys) SNV Uncertain significance 545697 rs771710305 GRCh37: 3:145809665-145809665
GRCh38: 3:146091878-146091878
22 PLOD2 NM_182943.3(PLOD2):c.533G>A (p.Arg178His) SNV Uncertain significance 343649 rs143513488 GRCh37: 3:145824401-145824401
GRCh38: 3:146106614-146106614
23 PLOD2 NM_182943.3(PLOD2):c.2121+14T>C SNV Uncertain significance 343644 rs376009508 GRCh37: 3:145788815-145788815
GRCh38: 3:146071028-146071028
24 PLOD2 NM_182943.3(PLOD2):c.*809T>C SNV Uncertain significance 343636 rs540984133 GRCh37: 3:145787695-145787695
GRCh38: 3:146069908-146069908
25 PLOD2 NM_182943.3(PLOD2):c.*1211C>T SNV Uncertain significance 343633 rs886058061 GRCh37: 3:145787293-145787293
GRCh38: 3:146069506-146069506
26 PLOD2 NM_182943.3(PLOD2):c.*1157T>C SNV Uncertain significance 343634 rs569145930 GRCh37: 3:145787347-145787347
GRCh38: 3:146069560-146069560
27 PLOD2 NM_000935.2(PLOD2):c.-322G>T SNV Uncertain significance 343658 rs550383313 GRCh37: 3:145879098-145879098
GRCh38: 3:146161311-146161311
28 PLOD2 NM_182943.3(PLOD2):c.*292C>T SNV Uncertain significance 343640 rs886058063 GRCh37: 3:145788212-145788212
GRCh38: 3:146070425-146070425
29 PLOD2 NM_182943.3(PLOD2):c.-95G>A SNV Uncertain significance 343655 rs368041250 GRCh37: 3:145878871-145878871
GRCh38: 3:146161084-146161084
30 PLOD2 NM_000935.2(PLOD2):c.-478G>C SNV Uncertain significance 343661 rs886058067 GRCh37: 3:145879254-145879254
GRCh38: 3:146161467-146161467
31 PLOD2 NM_182943.3(PLOD2):c.616-13T>A SNV Uncertain significance 343648 rs149019740 GRCh37: 3:145822142-145822142
GRCh38: 3:146104355-146104355
32 PLOD2 NM_182943.3(PLOD2):c.*683C>T SNV Uncertain significance 343638 rs566705549 GRCh37: 3:145787821-145787821
GRCh38: 3:146070034-146070034
33 PLOD2 NM_182943.3(PLOD2):c.-170C>G SNV Uncertain significance 343656 rs527384365 GRCh37: 3:145878946-145878946
GRCh38: 3:146161159-146161159
34 PLOD2 NM_182943.3(PLOD2):c.-81C>T SNV Uncertain significance 343654 rs886058065 GRCh37: 3:145878857-145878857
GRCh38: 3:146161070-146161070
35 PLOD2 NM_000935.2(PLOD2):c.-455C>T SNV Uncertain significance 343660 rs886058066 GRCh37: 3:145879231-145879231
GRCh38: 3:146161444-146161444
36 PLOD2 NM_182943.3(PLOD2):c.1732A>G (p.Ile578Val) SNV Uncertain significance 343645 rs558336915 GRCh37: 3:145791085-145791085
GRCh38: 3:146073298-146073298
37 PLOD2 NM_182943.3(PLOD2):c.*587G>A SNV Uncertain significance 343639 rs886058062 GRCh37: 3:145787917-145787917
GRCh38: 3:146070130-146070130
38 PLOD2 NM_182943.3(PLOD2):c.*148T>C SNV Uncertain significance 343642 rs886058064 GRCh37: 3:145788356-145788356
GRCh38: 3:146070569-146070569
39 PLOD2 NM_182943.3(PLOD2):c.471G>A (p.Val157=) SNV Uncertain significance 343650 rs761346369 GRCh37: 3:145828103-145828103
GRCh38: 3:146110316-146110316
40 PLOD2 NM_182943.3(PLOD2):c.306T>A (p.Asp102Glu) SNV Uncertain significance 343652 rs764056697 GRCh37: 3:145838931-145838931
GRCh38: 3:146121144-146121144
41 FKBP10 NM_021939.4(FKBP10):c.1149G>T (p.Arg383Ser) SNV Uncertain significance 982765 GRCh37: 17:39976606-39976606
GRCh38: 17:41820354-41820354
42 PLOD2 NM_182943.3(PLOD2):c.778-6T>G SNV Uncertain significance 981530 GRCh37: 3:145809694-145809694
GRCh38: 3:146091907-146091907
43 PLOD2 NM_182943.3(PLOD2):c.2270A>T (p.Asp757Val) SNV Uncertain significance 981531 GRCh37: 3:145788511-145788511
GRCh38: 3:146070724-146070724
44 PLOD2 NM_182943.3(PLOD2):c.1457A>G (p.Lys486Arg) SNV Uncertain significance 343647 rs760876151 GRCh37: 3:145796946-145796946
GRCh38: 3:146079159-146079159
45 PLOD2 NM_182943.3(PLOD2):c.1417C>T (p.Arg473Ter) SNV Uncertain significance 632404 rs750664256 GRCh37: 3:145796986-145796986
GRCh38: 3:146079199-146079199
46 PLOD2 NM_182943.3(PLOD2):c.836G>A (p.Cys279Tyr) SNV Uncertain significance 901869 GRCh37: 3:145809630-145809630
GRCh38: 3:146091843-146091843
47 PLOD2 NM_182943.3(PLOD2):c.*63T>G SNV Uncertain significance 902704 GRCh37: 3:145788441-145788441
GRCh38: 3:146070654-146070654
48 PLOD2 NM_182943.3(PLOD2):c.*25A>C SNV Uncertain significance 902706 GRCh37: 3:145788479-145788479
GRCh38: 3:146070692-146070692
49 PLOD2 NM_182943.3(PLOD2):c.335A>G (p.Glu112Gly) SNV Uncertain significance 902770 GRCh37: 3:145838902-145838902
GRCh38: 3:146121115-146121115
50 PLOD2 NM_182943.3(PLOD2):c.121G>A (p.Val41Ile) SNV Uncertain significance 902771 GRCh37: 3:145842005-145842005
GRCh38: 3:146124218-146124218

UniProtKB/Swiss-Prot genetic disease variations for Bruck Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 PLOD2 p.Arg598His VAR_022164 rs121434461
2 PLOD2 p.Gly601Val VAR_022165 rs121434460
3 PLOD2 p.Thr608Ile VAR_022166 rs121434459
4 PLOD2 p.Gly601Cys VAR_069531 rs762788421

Expression for Bruck Syndrome 2

Search GEO for disease gene expression data for Bruck Syndrome 2.

Pathways for Bruck Syndrome 2

GO Terms for Bruck Syndrome 2

Biological processes related to Bruck Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidyl-lysine hydroxylation GO:0017185 8.62 PLOD2 FKBP10

Sources for Bruck Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....