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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations

Johnston, Jennifer J.; Sapp, Julie C.; Turner, Joyce T.; Amor, David; Aftimos, Salim; Aleck, Kyrieckos A.; Bocian, Maureen; Bodurtha, Joann N.; Cox, Gerald F. and Curry, Cynthia J., et al. (2010) In Human Mutation 31(10). p.1142-1154
Abstract
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... (More)
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. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc. (Less)
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subject
keywords
Pallister-Hall syndrome, GLI3, Greig syndrome, oral-facial-digital, syndrome
in
Human Mutation
volume
31
issue
10
pages
1142 - 1154
publisher
John Wiley & Sons
external identifiers
  • wos:000282653900008
  • scopus:79251474031
ISSN
1059-7794
DOI
10.1002/humu.21328
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English
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yes
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49f52110-ad19-426b-ad84-96779cc945b2 (old id 1727165)
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2010-12-01 13:22:50
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@article{49f52110-ad19-426b-ad84-96779cc945b2,
  abstract     = {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. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.},
  author       = {Johnston, Jennifer J. and Sapp, Julie C. and Turner, Joyce T. and Amor, David and Aftimos, Salim and Aleck, Kyrieckos A. and Bocian, Maureen and Bodurtha, Joann N. and Cox, Gerald F. and Curry, Cynthia J. and Day, Ruth and Donnai, Dian and Field, Michael and Fujiwara, Ikuma and Gabbett, Michael and Gal, Moran and Graham, John M., Jr. and Hedera, Peter and Hennekam, Raoul C. M. and Hersh, Joseph H. and Hopkin, Robert J. and Kayserili, Hulya and Kidd, Alexa M. J. and Kimonis, Virginia and Lin, Angela E. and Lynch, Sally Ann and Maisenbacher, Melissa and Mansour, Sahar and McGaughran, Julie and Mehta, Lakshmi and Murphy, Helen and Raygada, Margarita and Robin, Nathaniel H. and Rope, Alan F. and Rosenbaum, Kenneth N. and Schaefer, G. Bradley and Shealy, Amy and Smith, Wendy and Soller, Maria and Sommer, Annmarie and Stalker, Heather J. and Steiner, Bernhard and Stephan, Mark J. and Tilstra, David and Tomkins, Susan and Trapane, Pamela and Tsai, Anne Chun-Hui and Van Allen, Margot I. and Vasudevan, Pradeep C. and Zabel, Bernhard and Zunich, Janice and Black, Graeme C. M. and Biesecker, Leslie G.},
  issn         = {1059-7794},
  keyword      = {Pallister-Hall syndrome,GLI3,Greig syndrome,oral-facial-digital,syndrome},
  language     = {eng},
  number       = {10},
  pages        = {1142--1154},
  publisher    = {John Wiley & Sons},
  series       = {Human Mutation},
  title        = {Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations},
  url          = {http://dx.doi.org/10.1002/humu.21328},
  volume       = {31},
  year         = {2010},
}