Tags

Type your tag names separated by a space and hit enter

Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1.
J Bone Joint Surg Am. 2011 Jun 01; 93(11):1045-50.JB

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 F437I 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 may be needed to confirm the importance of the hundreds of identified variants.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Washington University School of Medicine, 1 Children's Place, St. Louis, MO 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21531865

Citation

Alvarado, David M., et al. "Exome Sequencing Identifies an MYH3 Mutation in a Family With Distal Arthrogryposis Type 1." The Journal of Bone and Joint Surgery. American Volume, vol. 93, no. 11, 2011, pp. 1045-50.
Alvarado DM, Buchan JG, Gurnett CA, et al. Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1. J Bone Joint Surg Am. 2011;93(11):1045-50.
Alvarado, D. M., Buchan, J. G., Gurnett, C. A., & Dobbs, M. B. (2011). Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1. The Journal of Bone and Joint Surgery. American Volume, 93(11), 1045-50. https://doi.org/10.2106/JBJS.J.02004
Alvarado DM, et al. Exome Sequencing Identifies an MYH3 Mutation in a Family With Distal Arthrogryposis Type 1. J Bone Joint Surg Am. 2011 Jun 1;93(11):1045-50. PubMed PMID: 21531865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1. AU - Alvarado,David M, AU - Buchan,Jillian G, AU - Gurnett,Christina A, AU - Dobbs,Matthew B, PY - 2011/5/3/entrez PY - 2011/5/3/pubmed PY - 2011/10/11/medline SP - 1045 EP - 50 JF - The Journal of bone and joint surgery. American volume JO - J Bone Joint Surg Am VL - 93 IS - 11 N2 - 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 F437I 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 may be needed to confirm the importance of the hundreds of identified variants. SN - 1535-1386 UR - https://www.unboundmedicine.com/medline/citation/21531865/Exome_sequencing_identifies_an_MYH3_mutation_in_a_family_with_distal_arthrogryposis_type_1_ L2 - https://doi.org/10.2106/JBJS.J.02004 DB - PRIME DP - Unbound Medicine ER -