CLEIDOCRANIAL DYSPLASIA
RUNX2 Sequencing
DNA ANALYSIS

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder characterized by short stature, delayed closure of cranial fontanels and sutures, Wormian bones, frontal bossing, supernumery and late erupting secondary dentition, rudimentary or absent clavicles, wide pubic symphysis, generalized osteoporosis and other skeletal anomalies. The phenotypic spectrum is extremely variable even within families. The locus for CCD is on chromosome 6p21, which contains the RUNX2 gene. RUNX2 codes for a protein that is part of a transcription factor complex important for osteoblast differentiation. CCD patients show a variety of RUNX2 mutations. Most of these can be identified by sequencing, although large deletions or chromosomal translocations/inversions have been described. Patients with typical clinical features of CCD but without identifiable mutations in RUNX2 have also been described. Sequence analysis of the entire RUNX2 gene associated with Cleidocranial dysplasia is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine.

Reasons for Referral:

Confirmation of clinical diagnosis of Cleidocranial dysplasia.
Analysis of at-risk family members for identified mutations. Population carrier screening not offered.
Prenatal diagnosis (known mutation only).

Testing Methodology:

Full Sequencing: A PCR-based assay is used to amplify all 8 exons of the RUNX2 gene. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Sensitivity:

Clinical: Approximately 80%
Analytical: > 98%

Specimen Requirements:

Blood for DNA: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83904x16, 83912, 83909x16, 83898x8, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Otto F, Kanegane H, Mundlos S. (2002) Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum. Mutat. 19: 209-216.

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6150
Known Familial Mutation: 6151
Prenatal (Known Familial Mutation Only): 6152