distal arthrogryposis
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Classification
DA1: distal arthrogryposis type 1 (MIM.108120)
DA2A: distal arthrogryposis type 2A (MIM.193700)
DA2B: distal arthrogryposis type 2B (ch. 11) (MIM.601680)
DA2C: distal arthrogryposis type 2C
DA2D: distal arthrogryposis type 2D
DA3: distal arthrogryposis type 3 (Gordon syndrome) (MIM.114300) (camptodactyly, cleft palate and club-foot)
DA4: distal arthrogryposis type 4
DA5: distal arthrogryposis type 5
Etiology
mutations in TNNI2 (12592607)
- TNNI2 encodes an isoform of troponin I; this isoform and the isoforms of troponin T (TnT) and troponin C constitute the troponin complex of fast-twitch myofibers. This complex is the primary sensor of intracellular Ca+2 ion concentration in skeletal muscle, and, consequently, it is an important regulator of muscle contraction.
mutations in TPM2
TNNT3 (gene encoding TnT specific to fast-twitch myofibers) (DA2B) (12865991)
in syndromes
- Prader-Willi syndrome (15510104)
- velocardiofacial syndrome (15346917, 15042364)
- mosaic tetrasomy 10p (12599193)
- Proteus syndrome (9457508)
The troponin complex of fast-twitch myofibers exerts its effect on muscle contraction by binding to actin and beta-tropomyosin, the product encoded by TPM2 (Clark et al. 2002).
References
Bamshad M, Jorde LB, Carey JC. A revised and extended classification of the distal arthrogryposes. Am J Med Genet. 1996 Nov 11;65(4):277-81. PMID: 8923935