CFNS Clinical Trial
Official title:
Genetic Analysis of Craniofrontonasal Syndrome
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.
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.
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