BDA2
MCID: BRC079
MIFTS: 48

Brachydactyly, Type A2 (BDA2)

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

Aliases & Classifications for Brachydactyly, Type A2

MalaCards integrated aliases for Brachydactyly, Type A2:

Name: Brachydactyly, Type A2 57 13 55 40 73
Brachydactyly Type A2 12 76 53 59 44 15
Mohr-Wriedt Type Brachydactyly 57 12 53 75
Bda2 57 12 53 75
Brachymesophalangy Ii 57 12 75
Type A2 Brachydactyly 29 6
Brachydactyly, Mohr-Wriedt Type 59
Brachymesophalangy Type 2 53
Brachymesophalangy 2 53
Brachydactyly A2 75

Characteristics:

Orphanet epidemiological data:

59
brachydactyly type a2
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
brachydactyly, type a2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 112600
Disease Ontology 12 DOID:0110965
Orphanet 59 ORPHA93396
MESH via Orphanet 45 C537089
UMLS via Orphanet 74 C1832702
ICD10 via Orphanet 34 Q73.8
MedGen 42 C1832702
UMLS 73 C1832702

Summaries for Brachydactyly, Type A2

NIH Rare Diseases : 53 Brachydactyly type A2 is a very rare condition affecting the middle bone (middle phalanx) of the index finger and the second toe. Typically, people affected by brachydactyly type A2 have very short (hypoplastic) middle bones of these digits. In some individuals, the bone above the middle phalanx (distal phalanx) is shifted as well, so that the fingers and toes may look misshapen. There have not been reports of other symptoms associated with brachydactyly type A2. Typically, brachydactyly type A2 does not require surgery, and affected individuals are able to use their hands normally.

MalaCards based summary : Brachydactyly, Type A2, also known as brachydactyly type a2, is related to brachydactyly and brachydactyly, type c. An important gene associated with Brachydactyly, Type A2 is GDF5 (Growth Differentiation Factor 5), and among its related pathways/superpathways are Degradation of the extracellular matrix and Human Embryonic Stem Cell Pluripotency. Affiliated tissues include bone, heart and lymph node, and related phenotypes are short foot and clinodactyly of the 5th finger

Disease Ontology : 12 A brachydactyly characterized by autosomal dominant inheritance of malformations of the middle phalanx of the index finger and anomalies of the second toe that has material basis in heterozygous mutation in the BMPR1B gene on chromosome 4q or in the GDF5 gene on chromosome 20q11 or heterozygous duplication in a regulatory element of BMP2 on chromosome 20p12.

OMIM : 57 Brachydactyly type A2 is an autosomal dominant disorder characterized by malformations of the middle phalanx of the index finger and by anomalies of the second toe (summary by Su et al., 2011). (112600)

UniProtKB/Swiss-Prot : 75 Brachydactyly A2: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially.

Wikipedia : 76 Brachydactyly (Greek βρα�?ύ�? = "short" plus δάκ�?�?λο�? = "finger"), is a medical term which literally... more...

Related Diseases for Brachydactyly, Type A2

Diseases in the Brachydactyly family:

Brachydactyly, Type A1 Brachydactyly, Type A2
Brachydactyly, Type A3 Brachydactyly, Type A4
Brachydactyly, Type B1 Brachydactyly, Type C
Brachydactyly, Type D Brachydactyly, Type E1
Brachydactyly, Type A1, B Brachydactyly, Type B2
Brachydactyly, Type E2 Brachydactyly, Type A1, C
Brachydactyly, Type A1, D Brachydactyly Type A5
Brachydactyly Type A7

Diseases related to Brachydactyly, Type A2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 brachydactyly 30.3 ROR2 NOG IHH GDF5 BMPR1B BMP2
2 brachydactyly, type c 30.0 ROR2 NOG GDF5 BMPR1B
3 brachydactyly, type a2, with microcephaly 12.3
4 brachydactyly, type a4 11.5
5 brachydactyly type a7 11.2
6 acromesomelic dysplasia 10.2 GDF5 BMPR1B
7 acromesomelic dysplasia, hunter-thompson type 10.2 GDF5 BMPR1B
8 chondrodysplasia, grebe type 10.2 GDF5 BMPR1B
9 synostoses, tarsal, carpal, and digital 10.2 NOG GDF5
10 symphalangism, proximal, 1a 10.1 ROR2 NOG
11 tarsal-carpal coalition syndrome 10.1 ROR2 NOG
12 synovial chondromatosis 10.1 NOG BMP2
13 osseous heteroplasia, progressive 10.1 NOG BMP2
14 fibular hypoplasia and complex brachydactyly 10.1 NOG GDF5 BMPR1B
15 osteochondroma 10.1 BMPR1B BMP2
16 brachydactyly, type b2 10.1 ROR2 NOG GDF5
17 cerebral amyloid angiopathy, itm2b-related, 2 10.1 ITM2B FURIN
18 degenerative disc disease 10.1 GDF5 BMP2
19 cerebral amyloid angiopathy, itm2b-related, 1 10.0 ITM2B FURIN
20 brachydactyly, type b1 10.0 ROR2 NOG IHH
21 squamous cell papilloma 10.0 CYP2E1 BMP2
22 frozen shoulder 10.0 MMP3 GDF5
23 brachydactyly, type a1 10.0 ROR2 IHH GDF5 BMPR1B
24 fibrodysplasia ossificans progressiva 9.9 NOG BMPR1A
25 spondylolisthesis 9.9 MMP3 GDF5 BMP2
26 bone deterioration disease 9.9 MMP3 GDF5 BMP2
27 bone structure disease 9.9 MMP3 GDF5 BMP2
28 multiple synostoses syndrome 9.8 BMPR1B BMPR1A PAEP NOG GDF5
29 proximal symphalangism 9.8 ROR2 PAEP NOG GDF5 BMPR1B

Graphical network of the top 20 diseases related to Brachydactyly, Type A2:



Diseases related to Brachydactyly, Type A2

Symptoms & Phenotypes for Brachydactyly, Type A2

Symptoms via clinical synopsis from OMIM:

57
Skeletal Hands:
brachydactyly
medially deviated index finger
short index finger
variable fifth finger clinodactyly
hypoplastic/aplastic middle phalanx (2nd finger)
more
Skeletal Feet:
short, broad laterally deviated halluces
medially deviated second toe
syndactyly (2-3)


Clinical features from OMIM:

112600

Human phenotypes related to Brachydactyly, Type A2:

59 32 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short foot 59 32 frequent (33%) Frequent (79-30%) HP:0001773
2 clinodactyly of the 5th finger 59 32 frequent (33%) Frequent (79-30%) HP:0004209
3 short middle phalanx of the 5th finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0004220
4 short 2nd metacarpal 59 32 occasional (7.5%) Occasional (29-5%) HP:0010038
5 type a2 brachydactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0009372
6 aplasia/hypoplasia of the middle phalanx of the 2nd finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0009568
7 hallux valgus 32 HP:0001822
8 short hallux 32 HP:0010109
9 2-3 toe syndactyly 32 HP:0004691
10 short 2nd finger 32 HP:0009536
11 short middle phalanx of finger 59 Occasional (29-5%)
12 radial deviation of the 2nd finger 32 HP:0009467
13 broad hallux 32 HP:0010055
14 medially deviated second toe 32 HP:0008096
15 aplasia/hypoplasia of the middle phalanx of the 5th finger 32 HP:0009161
16 triangular shaped middle phalanx of the 5th finger 32 HP:0009182
17 ulnar deviation of the 2nd finger 32 HP:0009464
18 triangular shaped middle phalanx of the 2nd finger 32 HP:0009575

GenomeRNAi Phenotypes related to Brachydactyly, Type A2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell viability after pRB stimulation GR00230-A-1 8.8 BMPR1A BMPR1B ROR2

MGI Mouse Phenotypes related to Brachydactyly, Type A2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.95 BMP2 BMPR1A CYP2E1 FURIN IHH NOG
2 embryo MP:0005380 9.87 BMP2 BMPR1A BMPR1B FURIN IHH NOG
3 limbs/digits/tail MP:0005371 9.86 BMP2 BMPR1A BMPR1B FURIN GDF5 IHH
4 craniofacial MP:0005382 9.85 BMP2 BMPR1A BMPR1B IHH NOG ROR2
5 mortality/aging MP:0010768 9.85 BMP2 BMPR1A BMPR1B CYP2E1 FURIN GDF5
6 nervous system MP:0003631 9.61 BMP2 BMPR1A BMPR1B FURIN IHH ITM2B
7 skeleton MP:0005390 9.28 BMP2 BMPR1A BMPR1B GDF5 IHH MMP3

Drugs & Therapeutics for Brachydactyly, Type A2

Search Clinical Trials , NIH Clinical Center for Brachydactyly, Type A2

Cochrane evidence based reviews: brachydactyly type a2

Genetic Tests for Brachydactyly, Type A2

Genetic tests related to Brachydactyly, Type A2:

# Genetic test Affiliating Genes
1 Type A2 Brachydactyly 29 BMP2 BMPR1B GDF5

Anatomical Context for Brachydactyly, Type A2

MalaCards organs/tissues related to Brachydactyly, Type A2:

41
Bone, Heart, Lymph Node

Publications for Brachydactyly, Type A2

Articles related to Brachydactyly, Type A2:

# Title Authors Year
1
A novel duplication downstream of BMP2 in a Chinese family with Brachydactyly type A2 (BDA2). ( 29129813 )
2018
2
Identification of duplication downstream of BMP2 in a Chinese family with brachydactyly type A2 (BDA2). ( 24710560 )
2014
3
A 4.6 kb genomic duplication on 20p12.2-12.3 is associated with brachydactyly type A2 in a Chinese family. ( 21357617 )
2011
4
Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2. ( 19327734 )
2009
5
Brachydactyly type A2 associated with a defect in proGDF5 processing. ( 18203755 )
2008
6
A novel R486Q mutation in BMPR1B resulting in either a brachydactyly type C/symphalangism-like phenotype or brachydactyly type A2. ( 16957682 )
2006
7
A mutation in the receptor binding site of GDF5 causes Mohr-Wriedt brachydactyly type A2. ( 16014698 )
2006
8
Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. ( 16127465 )
2005
9
Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2. ( 14523231 )
2003

Variations for Brachydactyly, Type A2

UniProtKB/Swiss-Prot genetic disease variations for Brachydactyly, Type A2:

75
# Symbol AA change Variation ID SNP ID
1 BMPR1B p.Ile200Lys VAR_023819 rs121434417
2 BMPR1B p.Arg486Trp VAR_023820 rs121434418
3 BMPR1B p.Arg486Gln VAR_037967 rs121434419
4 GDF5 p.Leu441Pro VAR_017408 rs28936683
5 GDF5 p.Arg380Gln VAR_046743

ClinVar genetic disease variations for Brachydactyly, Type A2:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 BMPR1B NM_001203.2(BMPR1B): c.599T> A (p.Ile200Lys) single nucleotide variant Pathogenic rs121434417 GRCh37 Chromosome 4, 96051026: 96051026
2 BMPR1B NM_001203.2(BMPR1B): c.599T> A (p.Ile200Lys) single nucleotide variant Pathogenic rs121434417 GRCh38 Chromosome 4, 95129875: 95129875
3 BMPR1B NM_001203.2(BMPR1B): c.1456C> T (p.Arg486Trp) single nucleotide variant Pathogenic rs121434418 GRCh37 Chromosome 4, 96075771: 96075771
4 BMPR1B NM_001203.2(BMPR1B): c.1456C> T (p.Arg486Trp) single nucleotide variant Pathogenic rs121434418 GRCh38 Chromosome 4, 95154620: 95154620
5 BMPR1B NM_001203.2(BMPR1B): c.1457G> A (p.Arg486Gln) single nucleotide variant Pathogenic rs121434419 GRCh37 Chromosome 4, 96075772: 96075772
6 BMPR1B NM_001203.2(BMPR1B): c.1457G> A (p.Arg486Gln) single nucleotide variant Pathogenic rs121434419 GRCh38 Chromosome 4, 95154621: 95154621
7 GDF5 NM_000557.4(GDF5): c.1322T> C (p.Leu441Pro) single nucleotide variant Pathogenic rs28936683 GRCh37 Chromosome 20, 34021891: 34021891
8 GDF5 NM_000557.4(GDF5): c.1322T> C (p.Leu441Pro) single nucleotide variant Pathogenic rs28936683 GRCh38 Chromosome 20, 35434093: 35434093
9 BMP2 BMP2, 2.1-KB DUP, +110 KB duplication Pathogenic
10 GDF5 NM_000557.4(GDF5): c.1139G> A (p.Arg380Gln) single nucleotide variant Pathogenic rs397514668 GRCh37 Chromosome 20, 34022074: 34022074
11 GDF5 NM_000557.4(GDF5): c.1139G> A (p.Arg380Gln) single nucleotide variant Pathogenic rs397514668 GRCh38 Chromosome 20, 35434276: 35434276
12 Pathogenic NC_000005.10: g.104486890_104506841del19952 deletion 0 rsRCV000033864 Chromosome 5, 103822591:103842542 40972
13 Pathogenic NC_000005.10: g.104486890_104506841del19952 deletion 0 rsRCV000033864 Chromosome 5, 104486890:104506841 40972
14 Pathogenic 17q21.31 Microdeletion deletion 0 rsRCV000033866 40974
15 BMPR1B NM_001203.2(BMPR1B): c.705C> T (p.Thr235=) single nucleotide variant Benign/Likely benign rs56083112 GRCh37 Chromosome 4, 96051132: 96051132
16 BMPR1B NM_001203.2(BMPR1B): c.705C> T (p.Thr235=) single nucleotide variant Benign/Likely benign rs56083112 GRCh38 Chromosome 4, 95129981: 95129981
17 BMPR1B NM_001203.2(BMPR1B): c.*141C> T single nucleotide variant Benign rs1434536 GRCh37 Chromosome 4, 96075965: 96075965
18 BMPR1B NM_001203.2(BMPR1B): c.*141C> T single nucleotide variant Benign rs1434536 GRCh38 Chromosome 4, 95154814: 95154814
19 BMPR1B NM_001203.2(BMPR1B): c.1112G> A (p.Arg371Gln) single nucleotide variant Uncertain significance rs34970181 GRCh37 Chromosome 4, 96069934: 96069934
20 BMPR1B NM_001203.2(BMPR1B): c.1112G> A (p.Arg371Gln) single nucleotide variant Uncertain significance rs34970181 GRCh38 Chromosome 4, 95148783: 95148783
21 BMPR1B NM_001203.2(BMPR1B): c.640C> A (p.Arg214Ser) single nucleotide variant Pathogenic GRCh37 Chromosome 4, 96051067: 96051067
22 BMPR1B NM_001203.2(BMPR1B): c.640C> A (p.Arg214Ser) single nucleotide variant Pathogenic GRCh38 Chromosome 4, 95129916: 95129916
23 BMPR1B NM_001203.2(BMPR1B): c.430T> C (p.Leu144=) single nucleotide variant Likely benign rs55980670 GRCh38 Chromosome 4, 95123890: 95123890
24 BMPR1B NM_001203.2(BMPR1B): c.430T> C (p.Leu144=) single nucleotide variant Likely benign rs55980670 GRCh37 Chromosome 4, 96045041: 96045041
25 BMPR1B NM_001203.2(BMPR1B): c.300C> T (p.Asn100=) single nucleotide variant Likely benign rs140499888 GRCh38 Chromosome 4, 95115738: 95115738
26 BMPR1B NM_001203.2(BMPR1B): c.300C> T (p.Asn100=) single nucleotide variant Likely benign rs140499888 GRCh37 Chromosome 4, 96036889: 96036889

Copy number variations for Brachydactyly, Type A2 from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 154928 20 5000000 9000000 Duplication BMP2 Brachydactyly type A2

Expression for Brachydactyly, Type A2

Search GEO for disease gene expression data for Brachydactyly, Type A2.

Pathways for Brachydactyly, Type A2

GO Terms for Brachydactyly, Type A2

Cellular components related to Brachydactyly, Type A2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.7 BMP2 FURIN GDF5 IHH ITM2B MMP3
2 receptor complex GO:0043235 9.43 BMPR1A BMPR1B ROR2
3 extracellular region GO:0005576 9.23 BMP2 FURIN GDF5 IHH ITM2B MMP3
4 HFE-transferrin receptor complex GO:1990712 8.96 BMPR1A BMPR1B

Biological processes related to Brachydactyly, Type A2 according to GeneCards Suite gene sharing:

(show all 40)
# Name GO ID Score Top Affiliating Genes
1 in utero embryonic development GO:0001701 9.84 BMP2 BMPR1A IHH NOG
2 negative regulation of canonical Wnt signaling pathway GO:0090090 9.81 BMP2 NOG ROR2
3 osteoblast differentiation GO:0001649 9.8 BMP2 IHH NOG
4 transforming growth factor beta receptor signaling pathway GO:0007179 9.78 BMPR1A BMPR1B FURIN GDF5
5 positive regulation of epithelial cell proliferation GO:0050679 9.75 BMPR1A IHH NOG
6 positive regulation of osteoblast differentiation GO:0045669 9.73 BMP2 BMPR1A BMPR1B
7 SMAD protein signal transduction GO:0060395 9.72 BMP2 GDF5 ROR2
8 skeletal system development GO:0001501 9.72 BMP2 BMPR1B IHH NOG ROR2
9 pattern specification process GO:0007389 9.71 BMPR1A BMPR1B IHH NOG
10 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.7 BMP2 BMPR1A GDF5
11 dorsal/ventral pattern formation GO:0009953 9.69 BMPR1A BMPR1B NOG
12 bone mineralization GO:0030282 9.68 BMP2 ROR2
13 epithelial to mesenchymal transition GO:0001837 9.68 BMP2 NOG
14 collagen catabolic process GO:0030574 9.68 FURIN MMP3
15 mesoderm formation GO:0001707 9.67 BMPR1A NOG
16 positive regulation of bone mineralization GO:0030501 9.67 BMP2 BMPR1A BMPR1B
17 embryonic digit morphogenesis GO:0042733 9.67 BMPR1A IHH NOG ROR2
18 endoderm development GO:0007492 9.66 BMPR1A NOG
19 pituitary gland development GO:0021983 9.66 BMPR1A NOG
20 positive regulation of pri-miRNA transcription by RNA polymerase II GO:1902895 9.65 BMP2 BMPR1A
21 positive regulation of mesenchymal cell proliferation GO:0002053 9.65 BMPR1A IHH
22 positive regulation of chondrocyte differentiation GO:0032332 9.65 BMPR1B GDF5
23 cartilage condensation GO:0001502 9.64 BMPR1B ROR2
24 positive regulation of cartilage development GO:0061036 9.63 BMP2 BMPR1B
25 somite development GO:0061053 9.63 IHH NOG
26 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.63 BMPR1A BMPR1B GDF5
27 hindlimb morphogenesis GO:0035137 9.62 BMPR1A GDF5
28 mesenchymal cell differentiation GO:0048762 9.61 BMP2 NOG
29 pharyngeal arch artery morphogenesis GO:0061626 9.61 BMPR1A NOG
30 endocardial cushion morphogenesis GO:0003203 9.61 BMP2 BMPR1A NOG
31 proteoglycan metabolic process GO:0006029 9.6 BMP2 IHH
32 ventricular compact myocardium morphogenesis GO:0003223 9.59 BMPR1A NOG
33 BMP signaling pathway involved in heart development GO:0061312 9.58 BMPR1A NOG
34 chondrocyte differentiation GO:0002062 9.56 BMP2 BMPR1A BMPR1B GDF5
35 cellular response to BMP stimulus GO:0071773 9.46 BMP2 BMPR1A BMPR1B NOG
36 BMP signaling pathway GO:0030509 9.43 BMP2 BMPR1A BMPR1B GDF5 NOG ROR2
37 cartilage development GO:0051216 9.1 BMP2 BMPR1A BMPR1B GDF5 IHH NOG
38 positive regulation of transcription by RNA polymerase II GO:0045944 10.07 BMP2 BMPR1A BMPR1B IHH NOG
39 multicellular organism development GO:0007275 10.07 BMP2 IHH NOG PAEP ROR2
40 cell differentiation GO:0030154 10.04 BMP2 BMPR1A BMPR1B IHH NOG ROR2

Molecular functions related to Brachydactyly, Type A2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.92 BMPR1A BMPR1B CYP2E1 FURIN IHH MMP3
2 transforming growth factor beta-activated receptor activity GO:0005024 9.26 BMPR1A BMPR1B
3 transmembrane receptor protein serine/threonine kinase activity GO:0004675 9.16 BMPR1A BMPR1B
4 transforming growth factor beta receptor activity, type I GO:0005025 8.96 BMPR1A BMPR1B
5 SMAD binding GO:0046332 8.8 BMP2 BMPR1A BMPR1B

Sources for Brachydactyly, Type A2

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
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