Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations

Jennifer J. Johnston, Julie C. Sapp, Joyce T. Turner, David Amor, Salim Aftimos, Kyrieckos A. Aleck, Maureen Bocian, Joann N. Bodurtha, Gerald F. Cox, Cynthia J. Curry, Ruth Day, Dian Donnai, Michael Field, Ikuma Fujiwara, Michael Gabbett, Moran Gal, John M. Graham, Peter Hedera, Raoul C.M. Hennekam, Joseph H. HershRobert J. Hopkin, Hülya Kayserili, Alexa M.J. Kidd, Virginia Kimonis, Angela E. Lin, Sally Ann Lynch, Melissa Maisenbacher, Sahar Mansour, Julie Mcgaughran, Lakshmi Mehta, Helen Murphy, Margarita Raygada, Nathaniel H. Robin, Alan F. Rope, Kenneth N. Rosenbaum, G. Bradley Schaefer, Amy Shealy, Wendy Smith, Maria Soller, Annmarie Sommer, Heather J. Stalker, Bernhard Steiner, Mark J. Stephan, David Tilstra, Susan Tomkins, Pamela Trapane, Anne Chun Hui Tsai, Margot I. Van Allen, Pradeep C. Vasudevan, Bernhard Zabel, Janice Zunich, Graeme C.M. Black, Leslie G. Biesecker

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial-digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria.

Original languageEnglish (US)
Pages (from-to)1142-1154
Number of pages13
JournalHuman mutation
Issue number10
StatePublished - Oct 2010
Externally publishedYes


  • GLI3
  • Greig syndrome
  • Oral-facial-digital syndrome
  • Pallister-Hall syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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