Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome

Leslie G. Biesecker, Seongman Kang, Alejandro A. Schäffer, Margaret Abbott, Richard I. Kelley, Jeffrey C. Allen, Carol Clericuzio, Theresa Grebe, Ann Olney, John M. Graham

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than -2.0. We conclude that MD, USA hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus.

Original languageEnglish
Pages (from-to)947-951
Number of pages5
JournalJournal of Medical Genetics
Issue number11
Publication statusPublished - 1996
Externally publishedYes

Bibliographical note

Funding Information:
Financial support from DGICYT (PB91-0932) is also gratefully acknowledged.


  • Autosomal dominant inheritance
  • Hypothalamic hamartoma
  • Linkage analysis
  • Polydactyly

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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