Brachydactyly, Type C disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

NIH Rare Diseases:⁴⁸ Brachydactyly type c is a very rare congenital condition that is characterized by shortening of certain bones in the index, middle and little fingers. the bones of the ring finger are typically normal. other abnormalities may also be present such as hypersegmentation (extra bones) of the index and middle fingers; ulnar deviation (angled towards the fifth finger) of the index finger; and unusually-shaped bones and/or epiphysis (end of a long bone). brachydactyly type c is typically caused by changes (mutations) in the gdf5 gene and is inherited in an autosomal dominant manner. treatment varies based on the severity of the condition. physical therapy and/or plastic surgery may be indicated if the condition affects hand function. last updated: 11/4/2015

MalaCards based summary: Brachydactyly, Type C, also known as brachydactyly type c, is related to collecting duct carcinoma and bazex syndrome, and has symptoms including Array, Array and Array. An important gene associated with Brachydactyly, Type C is GDF5 (Growth Differentiation Factor 5), and among its related pathways are Hippo signaling pathway and TGF-beta signaling pathway (KEGG). Affiliated tissues include bone.

UniProtKB/Swiss-Prot:⁷⁰ Brachydactyly C: 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. Brachydactyly type C is characterized by deformity of the middle and proximal phalanges of the second and third fingers, sometimes with hypersegmentation of the proximal phalanx. The ring finger may be essentially normal and project beyond the others.

Disease Ontology:¹¹ A brachydactyly characterized by rachymesophalangy of the index, middle and little fingers, hyperphalangy of the index and middle finger, and shortening of the 1st metacarpal that has material basis in heterozygous mutation in the GDF5 gene on chromosome 20q11.

Description from OMIM:⁵² 113100

Related Diseases for Brachydactyly, Type C

Sources:
²⁰GeneAnalytics, ²¹GeneCards
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Diseases in the Brachydactyly family:

Brachydactyly, Type D	Brachydactyly, Type A1
Brachydactyly, Type A2	Brachydactyly, Type A1, B
Brachydactyly, Type B1	Brachydactyly, Type E2
Brachydactyly, Type B2	brachydactyly, type c
Brachydactyly, Type A1, C	Brachydactyly, Type E
Brachydactyly, Type A4	Brachydactyly Type A3
Brachydactyly Type A1d	Brachydactyly Type A5
Brachydactyly Type A7	Hoxd13-Related Brachydactyly
Brachydactyly of Toes

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

(show all 15)

id	Related Disease	Score	Top Affiliating Genes
1	collecting duct carcinoma	10.9
2	bazex syndrome	10.8
3	brachydactyly	10.3
4	symphalangism, proximal, 1b	9.9	BMPR1B, GDF5
5	multiple synostoses syndrome 2	9.9	BMPR1B, GDF5
6	glutamate formiminotransferase deficiency	9.9	BMPR1B, GDF5
7	charcot-marie-tooth disease type 7	9.9	BMPR1B, GDF5
8	tarsal-carpal coalition syndrome	9.9	BMPR1B, GDF5
9	cerebrotendinous xanthomatosis	9.9	BMPR1B, GDF5
10	immunodeficiency, common variable, 12	9.8	BMPR1B, GDF5
11	muscular dystrophy-dystroglycanopathy	9.8	BMPR1B, GDF5
12	multiple synostoses syndrome	9.8	BMPR1B, GDF5
13	androgenic alopecia	9.7	BMPR1B, GDF5
14	brachydactyly, type a2	9.7
15	proximal symphalangism	9.7

Graphical network of diseases related to Brachydactyly, Type C:

Symptoms & Phenotypes for Brachydactyly, Type C

Sources:
⁵²OMIM, ⁵⁴Orphanet, ⁶⁴The Human Phenotype Ontology
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Symptoms by clinical synopsis from OMIM:

113100

Clinical features from OMIM:

113100

Human phenotypes related to Brachydactyly, Type C:

⁵⁴ ⁶⁴ (show all 41)

id	Description	Orphanet Frequency	HPO Source Accession
1	abnormality of the fingernails⁶⁴ ⁵⁴	Frequent (79-30%)	HP:0001231
2	clinodactyly of the 5th finger⁶⁴ ⁵⁴	Occasional (29-5%)	HP:0004209
3	short stature⁶⁴ ⁵⁴	Occasional (29-5%)	HP:0004322
4	short middle phalanx of finger⁶⁴ ⁵⁴	Very frequent (99-80%)	HP:0005819
5	type c brachydactyly⁶⁴ ⁵⁴	Very frequent (99-80%)	HP:0009373
6	ulnar deviation of finger⁶⁴ ⁵⁴	Very frequent (99-80%)	HP:0009465
7	pseudoepiphyses of the 2nd finger⁶⁴ ⁵⁴	Very frequent (99-80%)	HP:0009495
8	complete duplication of distal phalanx of the thumb⁶⁴ ⁵⁴	Frequent (79-30%)	HP:0009606
9	stippling of the epiphysis of the distal phalanx of the thumb⁶⁴ ⁵⁴	Frequent (79-30%)	HP:0009684
10	symphalangism affecting the phalanges of the hand⁶⁴ ⁵⁴	Occasional (29-5%)	HP:0009773
11	aplasia/hypoplasia of the 1st metacarpal⁶⁴ ⁵⁴	Very frequent (99-80%)	HP:0010026
12	metatarsus valgus⁶⁴ ⁵⁴	Occasional (29-5%)	HP:0010508
13	cone-shaped epiphysis⁶⁴ ⁵⁴	Frequent (79-30%)	HP:0010579
14	short metatarsal⁶⁴ ⁵⁴	Frequent (79-30%)	HP:0010743
15	brachydactyly syndrome⁶⁴		HP:0001156
16	talipes equinovarus⁶⁴		HP:0001762
17	talipes equinovalgus⁶⁴		HP:0001772
18	delayed skeletal maturation⁶⁴		HP:0002750
19	madelung deformity⁶⁴		HP:0003067
20	hypersegmentation of proximal phalanx of second finger⁶⁴		HP:0006206
21	enlarged epiphysis of the middle phalanx of the 3rd finger⁶⁴		HP:0009324
22	triangular epiphysis of the middle phalanx of the 3rd finger⁶⁴		HP:0009331
23	enlarged epiphysis of the proximal phalanx of the 3rd finger⁶⁴		HP:0009349
24	triangular epiphysis of the proximal phalanx of the 3rd finger⁶⁴		HP:0009356
25	pseudoepiphyses of the 3rd finger⁶⁴		HP:0009417
26	triangular shaped middle phalanx of the 3rd finger⁶⁴		HP:0009436
27	triangular shaped proximal phalanx of the 3rd finger⁶⁴		HP:0009456
28	short 3rd finger⁶⁴		HP:0009461
29	ulnar deviation of the 3rd finger⁶⁴		HP:0009463
30	ulnar deviation of the 2nd finger⁶⁴		HP:0009464
31	enlarged epiphysis of the middle phalanx of the 2nd finger⁶⁴		HP:0009516
32	triangular epiphysis of the middle phalanx of the 2nd finger⁶⁴		HP:0009523
33	enlarged epiphysis of the proximal phalanx of the 2nd finger⁶⁴		HP:0009527
34	triangular epiphysis of the proximal phalanx of the 2nd finger⁶⁴		HP:0009534
35	short 2nd finger⁶⁴		HP:0009536
36	triangular shaped middle phalanx of the 2nd finger⁶⁴		HP:0009575
37	triangular shaped proximal phalanx of the 2nd finger⁶⁴		HP:0009587
38	short 1st metacarpal⁶⁴		HP:0010034
39	cone-shaped epiphyses of the middle phalanges of the hand⁶⁴		HP:0010259
40	polydactyly⁶⁴		HP:0010442
41	hypersegmentation of proximal phalanx of third finger⁶⁴		HP:0011929

Drugs & Therapeutics for Brachydactyly, Type C

Sources:
⁴ClinicalTrials, ⁷Cochrane Library, ⁴⁶NDF-RT, ⁶⁸UMLS
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Interventional clinical trials:

id	Name	Status	NCT ID	Phase
1	Study of Skeletal Disorders and Short Stature	Completed	NCT00001754

Search NIH Clinical Center for Brachydactyly, Type C

Cochrane evidence based reviews: brachydactyly type c

Genetic Tests for Brachydactyly, Type C

Sources:
²⁴GeneTests, ²⁷GTR
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Genetic tests related to Brachydactyly, Type C:

id	Genetic test	Affiliating Genes
1	Brachydactyly Type C²⁷ ²⁴	GDF5

Anatomical Context for Brachydactyly, Type C

Sources:
³⁶MalaCards
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MalaCards organs/tissues related to Brachydactyly, Type C:

³⁶

Bone

Publications for Brachydactyly, Type C

Sources:
⁵⁷PubMed
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Articles related to Brachydactyly, Type C:

(show all 20)

id	Title	Authors	Year
1	Brachydactyly Type C patient with compound heterozygosity for p.Gly319Val and p.Ile358Thr variants in the GDF5 proregion: benign variants or mutations? (25994865)	Stange K.... Seemann P.	2015
2	Two novel homozygous missense mutations in the GDF5 gene cause brachydactyly type C. (25820810)	Al-Qattan M.M.... Al Balwi M.A.	2015
3	Molecular analysis of two novel missense mutations in the GDF5 proregion that reduce protein activity and are associated with brachydactyly type C. (25092592)	Stange K.... Seemann P.	2014
4	Novel indel Mutation in the GDF5 Gene Is Associated with Brachydactyly Type C in a Four-Generation Turkish Family. (24715855)	Uyguner Z.O.... Kayserili H.	2014
5	Identification of a GDF5 mutation in a Korean patient with brachydactyly type C without foot involvement. (23483675)	Seo S.H.... Seong M.W.	2013
6	Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family. (23812741)	Farooq M.... Shimomura Y.	2013
7	A novel mutation in CDMP1 causes brachydactyly type C with 'angel- shaped phalanx'. A genotype-phenotype correlation in the mutational spectrum. (22828468)	Gutierrez-Amavizca B.E.... Barros-Nunez P.	2012
8	Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. (18283415)	Yang W.... Zhang X.	2008
9	A novel R486Q mutation in BMPR1B resulting in either a brachydactyly type C/symphalangism-like phenotype or brachydactyly type A2. (16957682)	Lehmann K.... Mundlos S.	2006
10	Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. (14735582)	Schwabe G.C.... Mundlos S.	2004
11	Severe aplastic anaemia in a child with brachydactyly type C. (12542502)	Svarch E.... Gale R.P.	2003
12	The mutational spectrum of brachydactyly type C. (12357473)	Everman D.B.... Warman M.L.	2002
13	Brachydactyly type C. (11172365)	Burgess R.C.	2001
14	Differences in complexity of isolated brachydactyly type C cannot be attributed to locus heterogeneity alone. (11169564)	Galjaard R.J.... Heutink P.	2001
15	Mutations in CDMP1 cause autosomal dominant brachydactyly type C. (9288091)	Polinkovsky A.... Warman M.L.	1997
16	Clinical and locus heterogeneity in brachydactyly type C. (9024575)	Robin N.H.... Morrison S.	1997
17	Brachydactyly type C gene maps to human chromsome 12q24. (8954778)	Polymeropoulos M.H.... Francomano C.A.	1996
18	Pitfalls of genetic counselling in brachydactyly type C. (7856649)	Camera G.... Mantero R.	1994
19	Brachydactyly type C associated with shortening of the hallux. (1583664)	Rowe-Jones J.M.... Patton M.A.	1992
20	Recessively inherited brachydactyly type C. (6842546)	Baraitser M.... Burn J.	1983

Genes related to Brachydactyly, Type C

Sources:
⁵Clinvar, ²¹GeneCards, ²⁴GeneTests, ⁵⁰Novoseek, ⁵²OMIM, ⁵⁴Orphanet, ⁷⁰UniProtKB/Swiss-Prot
See all MalaCards sources

Genes related to Brachydactyly, Type C (2 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

id	Symbol	Description	Score	Implication	PubmedIds
1	GDF5	Growth Differentiation Factor 5	1690.56	Molecular basis known ⁵² Pathogenic ⁵ Causative germline mutation (loss of function) ⁵⁴ Causative variation ⁷⁰ Genetic Tests ²⁴ Novoseek inferred ⁵⁰ GeneCards inferred via : Disorders, Publications (show sections)	12357473, 13953230, 14735582 more 12567410, 18283415, 12357473, 12567410, 14735582
2	BMPR1B	Bone Morphogenetic Protein Receptor Type 1B	52.91	Candidate gene tested ⁵⁴ GeneCards inferred via : Disorders, Publications (show sections)

Variations for Brachydactyly, Type C

Sources:
⁵Clinvar, ⁹dbSNP, ⁷⁰UniProtKB/Swiss-Prot
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UniProtKB/Swiss-Prot genetic disease variations for Brachydactyly, Type C:

⁷⁰

id	Symbol	AA change	Variation ID	SNP ID
1	GDF5	p.Met173Val	VAR_037978	rs28936397
2	GDF5	p.Thr201Pro	VAR_073139
3	GDF5	p.Leu263Pro	VAR_073140
4	GDF5	p.Thr203Asn	VAR_074161
5	GDF5	p.Val486Met	VAR_074162

Clinvar genetic disease variations for Brachydactyly, Type C:

⁵

id	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	GDF5	NM_ 000557.4(GDF5): c.1397G> A (p.Cys466Tyr)	SNV	Likely pathogenic	rs886039878	GRCh37	Chr 20, 34021816: 34021816
2	GDF5	NM_ 000557.4(GDF5): c.158delT (p.Leu53Argfs)	deletion	Pathogenic	rs886042462	GRCh37	Chr 20, 34025551: 34025551
3	GDF5	NM_ 000557.4(GDF5): c.901C> T (p.Arg301Ter)	SNV	Pathogenic	rs74315386	GRCh37	Chr 20, 34022312: 34022312
4	GDF5	GDF5, 23-BP INS, NT811	insertion	Pathogenic
5	GDF5	NM_ 000557.4(GDF5): c.517A> G (p.Met173Val)	SNV	Pathogenic	rs28936397	GRCh37	Chr 20, 34025192: 34025192
6	GDF5	GDF5, 1-BP INS, 206G	insertion	Pathogenic
7	GDF5	NM_ 000557.4(GDF5): c.1461T> G (p.Tyr487Ter)	SNV	Pathogenic	rs121909348	GRCh37	Chr 20, 34021752: 34021752

Expression for genes affiliated with Brachydactyly, Type C

Sources:
¹⁸Gene Expression Omnibus DataSets
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Search GEO for disease gene expression data for Brachydactyly, Type C.

Pathways for genes affiliated with Brachydactyly, Type C

Sources:
³⁴KEGG, ⁵⁵PathCards
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Pathways related to Brachydactyly, Type C according to GeneCards Suite gene sharing:

id	Super pathways	Score	Top Affiliating Genes
1	Hippo signaling pathway³⁴	9.1	BMPR1B, GDF5
2	TGF-beta signaling pathway (KEGG)³⁴ Show member pathways TGF-beta signaling pathway³⁴	9.1	BMPR1B, GDF5

GO Terms for genes affiliated with Brachydactyly, Type C

Sources:
¹⁹Gene Ontology
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Biological processes related to Brachydactyly, Type C according to GeneCards Suite gene sharing:

id	Name	GO ID	Score	Top Affiliating Genes
1	cartilage development	GO:0051216	9.6	BMPR1B, GDF5
2	chondrocyte differentiation	GO:0002062	9.6	BMPR1B, GDF5
3	positive regulation of chondrocyte differentiation	GO:0032332	9.5	BMPR1B, GDF5
4	transmembrane receptor protein serine/threonine kinase signaling pathway	GO:0007178	9.1	BMPR1B, GDF5