Phenotype and Etiology of Pallister-Hall Syndrome

Bisecker, L G.

Abstract

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.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HG000009-02
• Application #: 5203402
• Support Year: 2
• Fiscal Year: 1995

Institution

• Name: National Human Genome Research Institute
• Country: United States

Publications

Ng, David; Johnston, Jennifer J; Turner, Joyce T et al. (2004) Gonadal mosaicism in severe Pallister-Hall syndrome. Am J Med Genet A 124:296-302

Mykytyn, Kirk; Nishimura, Darryl Y; Searby, Charles C et al. (2003) Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1). Am J Hum Genet 72:429-37

Turner, Clesson; Killoran, Christina; Thomas, Nick S T et al. (2003) Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. Hum Genet 112:303-9

Biesecker, Leslie G (2003) Heritable syndromes with hypothalamic hamartoma and seizures: using rare syndromes to understand more common disorders. Epileptic Disord 5:235-8

Johnston, Jennifer J; Olivos-Glander, Isabelle; Turner, Joyce et al. (2003) Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am J Med Genet A 123:236-42

Biesecker, Leslie G (2002) Coupling genomics and human genetics to delineate basic mechanisms of development. Genet Med 4:39S-42S

Robin, N H; Biesecker, L G (2001) Considerations for a multiaxis nomenclature system for medical genetics. Genet Med 3:290-3

Killoran, C E; Abbott, M; McKusick, V A et al. (2000) Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis. Clin Genet 58:28-30

Stone, D L; Slavotinek, A; Bouffard, G G et al. (2000) Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome. Nat Genet 25:79-82

Slavotinek, A M; Stone, E M; Mykytyn, K et al. (2000) Mutations in MKKS cause Bardet-Biedl syndrome. Nat Genet 26:15-6