Malformations Clinical Trial
Official title:
Genetic and Clinical Studies of Congenital Anomaly Syndromes
We aim to delineate the range of severity, natural history, molecular etiology, and pathophysiology of Pallister-Hall syndrome (PHS), Greig cephalopolysyndactyly syndrome (GCPS), McKusick-Kaufman syndrome (MKS), Bardet-Biedl syndrome (BBS), Oro-facial digital syndromes (OFDs), and other overlapping phenotypes. These disorders comprise a syndrome community of overlapping manifestations and we hypothesize that this is a reflection of a common mechanistic pathway. This hypothesis be addressed by a combined clinical-molecular approach where we bring up to 50-100 patients with each disorder to the NIH clinical center for a comprehensive clinical evaluation with follow-up at a frequency appropriate to the disorder. Specimens will be collected and evaluated in the laboratory by linkage analysis, physical mapping, candidate gene characterization, mutation screening, and cell biologic studies of normal mutant proteins.
We aim to use the power of modern molecular genetics and clinical research to delineate the
range of severity, natural history, molecular etiology, and pathophysiology of a number of
congenital anomaly syndromes. The goal of the research is to develop a knowledge base that
allows proper clinical and molecular diagnosis of patients with rare congenital anomaly
disorders. Our paradigm is the previous work we have done with Pallister-Hall syndrome (PHS)
and Greig cephalopolysyndactyly syndrome (GCPS), where we have successfully used a combined
clinical-molecular approach. Using this strategy, we have brought 50-100 patients or families
with these disorders to the NIH clinical center (NIH CC) for a comprehensive clinical
evaluation with follow-up at a frequency appropriate to the disorder. We have also clinically
and/or molecularly evaluated many additional patients with atypical or non-classic
presentations of PHS and GCPS and have conducted exploratory studies of other phenotypes to
determine how they might fit into the more general models generated to explain PHS and GCPS.
We are currently generalizing this approach to a number of disorders including talipes
equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava
(TARP) syndrome. Specimens from patients participating in both the laboratory and clinical
arms of the protocol will be collected and evaluated in the laboratory by linkage analysis,
physical mapping, candidate gene characterization, mutation screening and targeted exome
sequencing, and cell biologic studies of normal and mutant proteins.
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Status | Clinical Trial | Phase | |
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Completed |
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