OSTEOGENESIS IMPERFECTA, AUTOSOMAL RECESSIVE
CRTAP Sequencing
DNA ANALYSIS

Osteogenesis imperfecta (OI) is a group of disorders characterized by brittle bones, Dentinogenesis imperfecta and hearing loss. The clinical spectrum of OI ranges from severe forms with perinatal lethality to milder presentations with some bone deformity and short or normal stature. OI manifests genetic heterogeneity with most cases of autosomal dominant OI being attributed to mutations in the type I collagen genes that cause abnormal fibril formation. Autosomal recessive forms of OI were shown to be associated with abnormal function of CASP and Leprecan proteins which are involved in posttranslational modification of collagen fibrils. Cartilage associated protein (CASP), encoded by the CRTAP gene on chromosome 3, forms a complex with Leprecan (P3H1) protein and is required for efficient 3-hydroxylation of fibrillar collagen prolyl residue. Loss of function mutations in the CRTAP gene cause abnormal bone formation and lead to OI . Diagnostic sequencing analysis of the CRTAP gene coding region is now being offered for OI patients and their at-risk relatives on a clinical basis.

Reasons for Referral:

Confirmation of diagnosis of Osteogenesis Imperfecta
Differentiation of autosomal recessive from autosomal dominant OI
Carrier testing in high-risk family members
Prenatal diagnosis in cases with a known familial mutation in the CRTAP gene

Testing Methodology:

PCR amplification of seven exons contained in the CRTAP gene coding region is performed on patient genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions using automated fluorescence dideoxy sequencing methods using capillary electrophoresis.

Sensitivity:

Analytical: ~99%

Specimen Requirements:

Blood for DNA: EDTA (purple-top) tubes: Adults: 14 cc; Child/Infant: 6 cc
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject, or their legal guardian, sign our consent form and submit it with the sample. To receive our forms and information about prenatal testing, please contact our laboratory.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83891, 83898X8, 83894, 83904x16, 83909x16, 83912
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894
Prenatal (Known Familial Mutation Only):83891x2, 83898x4, 83894x2, 83904x4, 83909x6, 83900x2, 83901x30, 83912x2

References:

1. Morello R, et al. (2006) Cell 127: 291-304

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6310
Known Familial Mutation: 6315
Prenatal (Known Familial Mutation Only): 6320