Genetic Analysis of Craniofrontonasal Syndrome
| Status: | Completed |
|---|---|
| Conditions: | Orthopedic |
| Therapuetic Areas: | Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2005 |
| End Date: | September 2008 |
This study will determine whether all patients with craniofrontonasal syndrome (CFNS) have a
mutation of a gene called ephrin-B1 (EFNB1). CFNS is one of a group of conditions called
craniosynostosis syndromes that result from closure of one or more of the fibrous joints
between the bones of the skull before brain growth is complete. Because of the premature
closure, the brain is not able to grow in its natural shape; instead, there is growth in
areas of the skull where the joints have not yet closed. In CFNS, it results in malformation
of the skull and face. It is known that the EFNB1 mutation can cause CFNS, and this study
will see if the gene change is present in all patients with the disorder.
This study includes patients and family members affected with CFNS. Participants have 1 to 2
teaspoons of blood drawn for genetic studies. A second blood sample may be requested for
further research. Some blood may be used to establish a cell line for later studies. This
involves growing the white blood cells from the blood sample. The cells can be kept in the
laboratory to make more DNA or can be frozen for later use in studies of craniosynostosis.
Patients may also have their medical records reviewed to relate gene changes to clinical
features in CFNS.
mutation of a gene called ephrin-B1 (EFNB1). CFNS is one of a group of conditions called
craniosynostosis syndromes that result from closure of one or more of the fibrous joints
between the bones of the skull before brain growth is complete. Because of the premature
closure, the brain is not able to grow in its natural shape; instead, there is growth in
areas of the skull where the joints have not yet closed. In CFNS, it results in malformation
of the skull and face. It is known that the EFNB1 mutation can cause CFNS, and this study
will see if the gene change is present in all patients with the disorder.
This study includes patients and family members affected with CFNS. Participants have 1 to 2
teaspoons of blood drawn for genetic studies. A second blood sample may be requested for
further research. Some blood may be used to establish a cell line for later studies. This
involves growing the white blood cells from the blood sample. The cells can be kept in the
laboratory to make more DNA or can be frozen for later use in studies of craniosynostosis.
Patients may also have their medical records reviewed to relate gene changes to clinical
features in CFNS.
The scientific objective of this study is to determine if all patients with
Craniofrontonasal Syndrome (CFNS) contain mutations in the ephrin-B1 (EFNB1) gene in Xq12.
We will use mutational analysis of EFNB1 as our principal tool to study the genetics of
CFNS. Previously, we had mapped the CFNS locus to a 13 cM region in Xp22 using linkage
analysis of 12 unrelated CFNS families with 2 or more affected family members in 2-4
generations. More recently there have been two reports that 23 independent CFNS patients all
have mutations in the EFNB1 located at Xq12. Hence, either CFNS displays genetic
heterogeneity with at least two genes (one in Xp22 and EFNB1) or our previous linkage
analysis was inaccurate and all CFNS patients have EFNB1 mutations.
We have previously collected a large number of coded blood samples from patients with DFNS.
We propose to sequence the EFNB1 in all 12 of our previously published CFNS families as well
as 6 additional families, 22 sporadic CFNS patients, and two CFNS patients with chromosomal
anomalies.
We will be sending letters to all physicians who have referred CFNS patients to us in the
past for molecular studies. This letter will outline the recent developments identifying
EFNB1 as the CFNS gene. We would like to utilize the referring physicians as liaisons
between our lab and CFNS patients. Through the referring physicians, we will invite the
patients and their families to join a new study if they are interested in obtaining their
genetic testing results. All of our results will be confirmed by a CLIA-certified lab prior
to being given to patients or referring physicians.
Craniofrontonasal Syndrome (CFNS) contain mutations in the ephrin-B1 (EFNB1) gene in Xq12.
We will use mutational analysis of EFNB1 as our principal tool to study the genetics of
CFNS. Previously, we had mapped the CFNS locus to a 13 cM region in Xp22 using linkage
analysis of 12 unrelated CFNS families with 2 or more affected family members in 2-4
generations. More recently there have been two reports that 23 independent CFNS patients all
have mutations in the EFNB1 located at Xq12. Hence, either CFNS displays genetic
heterogeneity with at least two genes (one in Xp22 and EFNB1) or our previous linkage
analysis was inaccurate and all CFNS patients have EFNB1 mutations.
We have previously collected a large number of coded blood samples from patients with DFNS.
We propose to sequence the EFNB1 in all 12 of our previously published CFNS families as well
as 6 additional families, 22 sporadic CFNS patients, and two CFNS patients with chromosomal
anomalies.
We will be sending letters to all physicians who have referred CFNS patients to us in the
past for molecular studies. This letter will outline the recent developments identifying
EFNB1 as the CFNS gene. We would like to utilize the referring physicians as liaisons
between our lab and CFNS patients. Through the referring physicians, we will invite the
patients and their families to join a new study if they are interested in obtaining their
genetic testing results. All of our results will be confirmed by a CLIA-certified lab prior
to being given to patients or referring physicians.
- INCLUSION CRITERIA:
CFNS patients and their families who were previously referred to us; the majority have DNA
samples and clinical data already archived in our collection.
EXCLUSION CRITERIA:
Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of
their children as minors) or assent.
We generally reviewed a brief clinical description from the referring physician about a
potential research subject to determine that the subject was appropriate to enter into the
study. We reserved the right to exclude cases that were clearly not related to our direct
research interests.
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