The Pallister-Hall Syndrome (PHS) includes polydactyly, anal atresia, hypospadias, and hypothalamic hamartoma. It is extremely rare but is interesting because of the developmental implications of such a spectrum of anomalies. There are several disorders that have related maformations that are thought to be genetically or morphogenetically related to PHS. These include Oral-Facial-Digital type VI, MuKusick-Kaufmann syndrome, and others. We have identified 4 families that segregate the PHS phenotype in an autosomal dominant pattern. We are performing clinical and molecular studies on these families to better define the range of phenotypic features in PHS and search for the gene by a linkage approach. To date we have clinically evaluated 10 individuals with PHS and have acquired DNA specimens on nearly 100 persons from families with this disorder. We have excluded several genetic loci that were hypothesized to be the location of the PHS gene and have definitive evidence for linkage to one region of the human genome. The next step of this project is to narrow the PHS locus and identify the gene or genes responsible.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Intramural Research (Z01)
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National Human Genome Research Institute
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