Phenotype and Etiology of Pallister/Hall Syndrome

Bisecker, L G.

Abstract

In the last fiscal year we determined the etiology of this disorder. It is caused by mutations in the GLI3 zinc finger transcription factor and is thus allelic to the Greig cephalopolysyndactyly syndrome. In this fiscal year we plan to determine mutations in additional families to perform genotype-phenotype correlation, study the intracellular distribution and transcriptional activation properties, and study animal models of the disorder. Our preliminary data show that the truncated mutant GLI3 protein has nuclear tageting by using green fluorescent protein tagged GLI3. In addition, we will study patients with Greig cephalopolysyndactyly syndrome to determine the clinical and molecular overlap of these disorders. We have preliminary data showing that microdeletions may be a common cause of Greig syndrome.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HG000009-04
• Application #: 6162544
• Study Section: Special Emphasis Panel (LGDR)
• Support Year: 4
• Fiscal Year: 1997

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

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

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

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