OSTEOGENESIS IMPERFECTA

Jordan Hansard

Genetics Presentation

http://www.beltina.org/health-dictionary/osteogenesis-imperfecta-types-treatment.html

Overview Mutations of COL1A1 or

COL1A2 Causes collagen

abnormalities Autosomal Dominant Broad range of

characteristics Occurs 6-7/100,000 births

worldwide Effects all people equally

History 1000 BC ancient mummuy 1788 Swede gives 1st scientific

description 1850s term Osteogenesis

imperfecta used 1979 Sillence clinical

classification 1983 Genetic knowledge acquired

(microray alaysis)

Genes Involved

COL1A1 Instructs making of type 1 collagen Produces pro-α1(I) chain

COL1A1 gene is located on the long (q) arm of chromosome 17

http://ghr.nlm.nih.gov/gene/COL1A1

Genes Involved Cont..:

COL1A2 Instructs making of type 1 collagen Produces pro-α2(I) chain

COL1A2 gene is located on the long (q) arm of chromosome 7

http://ghr.nlm.nih.gov/gene/COL1A2

Collagen Only type 1 collagen has been

associated with OI Type 1 collagen is the main protein

building block in bone, & connective tissues such as tendons and ligaments.

When there is a problem with the body’s production of type 1 collagen, the bones are brittle and break more easily than normal.

Characteristics of OI and Types

http://www.nejm.org/doi/full/10.1056/NEJMicm062996

Type 1

Most common Most fractures occur during

preschool years Deformity level is moderate Blue Sclera Nonlethal

http://media.morristechnology.com/mediafilesvr/upload/gainesville/article/2011/06/25/0626Coan_.jpg

Type 2

Most Extreme Highest death rate @ 90% Extreme bone fragility Blue sclera

http://otic.hawkelibrary.com/new/d/337-2/4_59_hr.jpg

http://childrenshospital.org/az/Site1390/Images/Thriving_Sandypic1.jpg

Type 3

Short stature Fractures at birth Gets worse with age Majority die before puberty

due to complications cause by OI

http://see.visualdx.com/diagnosis/osteogenesis_imperfecta.jpg

http://www.hss.edu/images/articles/fassier_duval_rods_OI_4_original.jpg

Type 4

Less severe than 3 Fractures less after puberty Short stature Nonlethal

http://adc.bmj.com/content/vol92/issue4/images/large/ac96552.f3.jpeg

Diagnosing OI Sillence Chart

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343766/figure/F8/

Prenatal Diagnose Ultrasonography

Prenatal ultrasonographic diagnosis of OI type I is unreliable

Sonographic signs of OI type II can be detected as early as 14 weeks

Chorion villus biopsy with cultured chorion villi cells Test for abnormal production of collagen type I (10-12 weeks)

Current Research Marrow Mesenchymal Cell Therapy for

Osteogenesis Imperfecta: A Pilot Study previous research found that children treated with bone

marrow transplant began to grow faster, had more minerals in their bones, and broke their bones less often than before the bone marrow transplant.

It is hoped that by removing the CD3+ cells from the donated bone marrow, the subject’s body will be infused quite safely and that body growth and bone strength will increase. The CD3+ cells will be removed from the donor bone marrow by use of a machine called the CliniMACS System. This machine has not been approved for use in the United States by the Food and Drug Administration (FDA). The use of this device is considered experimental.

Michael Kim, Jensen Law, Michael Lee, Shou Yi Poo (2004)

No Cure. Only Treatments

Fracture management Rodding surgery Bone marrow transplant Physical and occupational therapy to

maximize strength and function. bisphosphonate medications (such as

pamidronate, risedronate, alendronate and zoledronic acid) -----Successful?

Trying to silence mutations (Recent)

OI in the Media Samuel Jackson as Mr. Glass

“Unbreakable” Jeff "Joker" Moreau Mass effect pilot Atticus Shaffer from “The Middle Kid President on youtube.com

http://en.wikipedia.org/wiki/Kid_Presidenthttp://en.wikipedia.org/wiki/Atticus_Shaffer

References http://www.contempclindent.org/articles/2012/3/2/images/

ContempClinDent_2012_3_2_197_96822_t1.jpg

Aase JM. Diagnostic Dysmorphology. New York: Plenum Medical Book Company; 1990. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343766/

Alanay Y, Avaygan H, Camacho N, Utine GE, Boduroglu K, et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2010;86:551–559.

Baldridge D, Schwarze U, Morello R, Lennington J, Bertin TK, et al. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat. 2008;29:1435–1442. [

B. Willem Vrolik as a teratologist [in Dutch] Ned Tijdschr Geneeskd. 1984;128:1530–1534.

Baljet B. Aspects of the history of osteogenesis imperfecta (Vrolik's syndrome) Ann Anat. 2002;184:1–7.

Bank RA, Robins SP, Wijmenga C, Breslau-Siderius LJ, Bardoel AF, et al. Defective collagen cross-linking in bone, but not in ligament or cartilage, in Bruck syndrome: indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17. Proc Natl Acad Sci USA. 1999;96:1054–1058.

Lapunzina P, Aglan M, Temtamy S, Caparrós-Martin JA, Valencia M, et al. Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. Am J Hum Genet. 2010;87:110–114.

Philippi CA, Remmington T, Steiner RD. The Cochrane Collaboration. England: John Wiley & Sons Ltd.; 2009. Bisphosphonate therapy for osteogenesis imperfecta.

Steiner RD, Pepin MG, Byers PH. Osteogenesis Imperfecta, in Pagon RA, Bird TD, Dolan CR, Stephens K (eds): GeneReviews (University of Washington, Seattle 1993). http://www.ncbi.nlm.nih.gov/books/NBK1116/

http://www.oif.org/site/PageServer?pagename=TypeI

QUESTIONS

http://www.cdc.gov/niosh/docs/94-127/