Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8.

Abstract

Trismus-pseudocamptodactyly syndrome (TPS) is a rare autosomal dominant distal arthrogryposis (DA) characterized by an inability to open the mouth fully (trismus) and an unusual camptodactyly of the fingers that is apparent only upon dorsiflexion of the wrist (i.e., pseudocamptodactyly). TPS is also known as Dutch-Kentucky syndrome because a Dutch founder mutation is presumed to be the origin of TPS cases in the Southeast US, including Kentucky. To date only a single mutation, p.R674Q, in MYH8 has been reported to cause TPS. Several individuals with this mutation also had a so-called "variant" of Carney complex, suggesting that the pathogenesis of TPS and Carney complex might be shared. We screened MYH8 in four TPS pedigrees, including the original Dutch family in which TPS was reported. All four TPS families shared the p.R674Q substitution. However, haplotype analysis revealed that this mutation has arisen independently in North American and European TPS pedigrees. None of the individuals with TPS studied had features of Carney complex, and p.R674Q was not found in 49 independent cases of Carney complex that were screened. Our findings show that distal arthrogryposis syndromes share a similar pathogenesis and are, in general, caused by disruption of the contractile complex of muscle.

• Authors: Reha M Toydemir, Harold Chen, Virginia K Proud, Rick Martin, Hans van Bokhoven, Ben C J Hamel, Joep H Tuerlings, Constantine A Stratakis, Lynn B Jorde, Michael J Bamshad
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 140 Issue 22 Pg. 2387-93 (Nov 15 2006) ISSN: 1552-4825 [Print] United States
• PMID: 17041932 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: (c) 2006 Wiley-Liss, Inc.

Chemical References

• MYH8 protein, human
• DNA
• Myosin Heavy Chains

Topics

• Amino Acid Sequence
• Amino Acid Substitution
• Arthrogryposis (genetics)
• Base Sequence
• Conserved Sequence
• DNA (genetics)
• Female
• Genes, Dominant
• Haplotypes
• Humans
• Male
• Models, Molecular
• Mutation, Missense
• Myosin Heavy Chains (chemistry, genetics)
• Pedigree
• Sequence Homology, Amino Acid
• Syndrome
• Trismus (genetics)