Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome

Seong Man Kang, Jeffrey Allen, John M. Graham, Theresa Grebe, Carol Clericuzio, Nicholas Patronas, Frank Ondrey, Eric Green, Alejandro Schäffer, Margaret Abbott, Leslie G. Biesecker

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Pallister-Hall syndrome is a human developmental disorder that is inherited in an autosomal dominant pattern. The phenotypic features of the syndrome include hypothalamic hamartoma, polydactyly, imperforate anus, laryngeal clefting, and other anomalies. Here we describe the clinical characterisation of a family with 22 affected members and the genetic mapping of the corresponding locus. Clinical, radiographic, and endoscopic evaluations showed that this disorder is a fully penetrant trait with variable expressivity and low morbidity. By analysing 60 subjects in two families using anonymous STRP markers, we have established linkage to 7p13 by two point analysis with D7S691 resulting in a lod score of 7.0 at θ = 0, near the GLI3 locus. Deletions and translocations in GLI3 are associated with the Greig cephalopolysyndactyly syndrome. Although Greig cephalopolysyndactyly syndrome has some phenotypic overlap with Pallister-Hall syndrome, these two disorders are clinically distinct. The colocalisation of loci for these distinct phenotypes led us to analyse GLI3 for mutations in patients with Pallister-Hall syndrome. We have previously shown GLI3 mutations in two other small, moderately affected families with Pallister-Hall syndrome. The linkage data reported here suggest that these larger, mildly affected families may also have mutations in GLI3.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
JournalJournal of Medical Genetics
Volume34
Issue number6
Publication statusPublished - 1997 Jul 8
Externally publishedYes

Fingerprint

Pallister-Hall Syndrome
Chromosome Mapping
Mutation
Imperforate Anus
Polydactyly
Lod Score
Information Storage and Retrieval
Morbidity
Phenotype

Keywords

  • Epiglottis
  • Hypothalamic hamartoma
  • Linkage mapping
  • Polydactyly

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kang, S. M., Allen, J., Graham, J. M., Grebe, T., Clericuzio, C., Patronas, N., ... Biesecker, L. G. (1997). Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. Journal of Medical Genetics, 34(6), 441-446.

Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. / Kang, Seong Man; Allen, Jeffrey; Graham, John M.; Grebe, Theresa; Clericuzio, Carol; Patronas, Nicholas; Ondrey, Frank; Green, Eric; Schäffer, Alejandro; Abbott, Margaret; Biesecker, Leslie G.

In: Journal of Medical Genetics, Vol. 34, No. 6, 08.07.1997, p. 441-446.

Research output: Contribution to journalArticle

Kang, SM, Allen, J, Graham, JM, Grebe, T, Clericuzio, C, Patronas, N, Ondrey, F, Green, E, Schäffer, A, Abbott, M & Biesecker, LG 1997, 'Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome', Journal of Medical Genetics, vol. 34, no. 6, pp. 441-446.
Kang SM, Allen J, Graham JM, Grebe T, Clericuzio C, Patronas N et al. Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. Journal of Medical Genetics. 1997 Jul 8;34(6):441-446.
Kang, Seong Man ; Allen, Jeffrey ; Graham, John M. ; Grebe, Theresa ; Clericuzio, Carol ; Patronas, Nicholas ; Ondrey, Frank ; Green, Eric ; Schäffer, Alejandro ; Abbott, Margaret ; Biesecker, Leslie G. / Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. In: Journal of Medical Genetics. 1997 ; Vol. 34, No. 6. pp. 441-446.
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