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Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations
Author(s) -
Johnston Jennifer J.,
Sapp Julie C.,
Turner Joyce T.,
Amor David,
Aftimos Salim,
Aleck Kyrieckos A.,
Bocian Maureen,
Bodurtha Joann N.,
Cox Gerald F.,
Curry Cynthia J.,
Day Ruth,
Donnai Dian,
Field Michael,
Fujiwara Ikuma,
Gabbett Michael,
Gal Moran,
Graham John M.,
Hedera Peter,
Hennekam Raoul C.M.,
Hersh Joseph H.,
Hopkin Robert J.,
Kayserili Hülya,
Kidd Alexa M.J.,
Kimonis Virginia,
Lin Angela E.,
Lynch Sally Ann,
Maisenbacher Melissa,
Mansour Sahar,
McGaughran Julie,
Mehta Lakshmi,
Murphy Helen,
Raygada Margarita,
Robin Nathaniel H.,
Rope Alan F.,
Rosenbaum Kenneth N.,
Schaefer G. Bradley,
Shealy Amy,
Smith Wendy,
Soller Maria,
Sommer Annmarie,
Stalker Heather J.,
Steiner Bernhard,
Stephan Mark J.,
Tilstra David,
Tomkins Susan,
Trapane Pamela,
Tsai Anne ChunHui,
Van Allen Margot I.,
Vasudevan Pradeep C.,
Zabel Bernhard,
Zunich Janice,
Black Graeme C.M.,
Biesecker Leslie G.
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21328
Subject(s) - gli3 , proband , genetics , biology , phenotype , mutation , genotype , hum , genotype phenotype distinction , gene , repressor , art , performance art , transcription factor , art history
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. © 2010 Wiley‐Liss, Inc.