TITLE

Exome Sequencing Identifies an MYH3 Mutation in a Family with Distal ArthrogrypOsis Type 1

AUTHOR(S)
Alvarado, David M.; Buchan, Jilian G.; Gurnett, Christina A.; Dobbs, Matthew B.
PUB. DATE
June 2011
SOURCE
Journal of Bone & Joint Surgery, American Volume;6/1/2011, Vol. 93-A Issue 11, p1045
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Few genes responsible for distal arthrogryposis type 1 are known, although genes coding for the proteins in the sarcomere have been implicated in other types of distal arthrogryposis. Cost-effective sequencing methods are now available to examine all genes in the human genome for the purpose of establishing the genetic basis of musculoskeletal disorders. Methods: A multigenerational family with distal arthrogryposis type 1 characterized by clubfoot and mild hand contractures was identified, and exome sequencing was performed on DNA from one of the affected family members. Linkage' analysis was used to confirm whether a genetic variant segregated with distal arthrogryposis. Results: Exome sequencing identified 573 novel variants that were not present in control databases. A missense mutation in MYH3 (a gene coding for the heavy chain of myosin), causing an F4371 amino acid substitution, was identified that segregated with distal arthrogryposis in this family. Linkage analysis confirmed that this MYH3 mutation was the only exome variant common to all six affected individuals. Conclusions: Identification of an MYH3 mutation in this family with distal arthrogryposis type 1 broadens the phenotype associated with MYH3 mutations to include distal arthrogryposis types 1, 2A (Freeman-Sheldon syndrome), and 2B (Sheldon-Hall syndrome). Exome sequencing is a useful and cost-effective method to discover causative genetic mutations, although data from extended families maybe needed to confirm the importance of the hundreds of identified variants.
ACCESSION #
62548324

 

Related Articles

  • The discovery and confirmation of single nucleotide polymorphisms in the human p53R2 gene by EST database analysis. Zheng Ye; Parry, James M. // Mutagenesis;Sep2002, Vol. 17 Issue 5, p361 

    The human expressed sequence tag (EST) database provides a wealth of resources, which can be used to rapidly screen for potential polymorphisms in proteins of physiological interest. The human p53R2 gene, a recently identified ribonucleotide reductase, plays an important role in DNA repair and...

  • BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families. Claes, K.; Poppe, B.; Coene, I.; De Paepe, A.; Messiaen, L. // British Journal of Cancer;3/22/2004, Vol. 90 Issue 6, p1244 

    Worldwide variation in the distribution of BRCA1 and BRCA2 mutations is well recognised, and for the Belgian population no comprehensive studies about BRCA1/2 mutation spectra or frequencies have been published. We screened the complete coding region of both genes in 451 individuals from 349...

  • 390. Phage c31 Integrase Induces Chromosomal Aberrations in Primary Human Fibroblasts. Jian Liu; Jeppesen, Iben; Nielsen, Kate; Jensen, Thomas G. // Molecular Therapy;Jun2006, Vol. 13, pS149 

    Phage c31 integrase is a recombinase with the potential to perform site-specific integration into a host chromosome. The enzyme mediates recombination between two different short sequences of DNA, attP and attB recognition sites. In mouse and human genomes, phage c31 integrase mediates the...

  • The Deacetylase Sirtuin 1 Regulates Human Papillomavirus Replication by Modulating Histone Acetylation and Recruitment of DNA Damage Factors NBS1 and Rad51 to Viral Genomes. Langsfeld, Erika S.; Bodily, Jason M.; Laimins, Laimonis A. // PLoS Pathogens;9/25/2015, Vol. 11 Issue 9, p1 

    Human papillomaviruses (HPV) regulate their differentiation-dependent life cycles by activating a number of cellular pathways, such as the DNA damage response, through control of post-translational protein modification. Sirtuin 1 (SIRT1) is a protein deacetylase that modulates the acetylation of...

  • Gene explorers overlook Africa. Chen, Ingfei; Franklin, Deborah // Health (Time Inc. Health);Mar/Apr95, Vol. 9 Issue 2, p19 

    Reports on the assertion by a immunogeneticist that the Human Genome Project failed to include a representative sample of blacks. Project coverage as presently limited to deoxyribonucleic acid (DNA) from fair-skinned types; Planned inclusion of sample DNA from Asian peoples.

  • Whither the human genome project? Sinsheimer, R.L. // Hastings Center Report;Jul/Aug90, Vol. 20 Issue 4, p5 

    Highlights the issues raised by the human genome project. Access to genetic information; Eugenics.

  • Mapping and beyond.  // Hastings Center Report;Nov/Dec90, Vol. 20 Issue 6, p3 

    Reports that the Council for International Organizations of Medical Sciences convened a forum to consider the ethical, scientific, and social implications of the human genome project. Participants from thirty nations; Meeting in Japan; Broad implicit agreement of guiding principles; More.

  • Valencia, 1990. Yesley, M.S. // Hastings Center Report;Mar/Apr91, Vol. 21 Issue 2, p3 

    Discusses a workshop held last November in Valencia, Spain whose topic was international cooperation in ethical aspects of the Human Genome Project (HGP). National scientific and social policies on the HGP; Religious considerations; Impact of HGP on medicine and biology; Keynoter, Jack...

  • Whither the ELSI Program? Roberts, Leslie // Hastings Center Report;Nov/Dec93, Vol. 23 Issue 6, p5 

    Reports on the formation of an independent commission to oversee the ethical, legal, and social implications of the Human Genome Project. Budget cut on the already existing program with similar function, ELSI; Criticisms on ELSI as not being independent enough; Bureaucracy and inefficiency of...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics