Tags

Type your tag names separated by a space and hit enter

Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations.
Hum Mutat. 2010 Oct; 31(10):1142-54.HM

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.

Authors+Show Affiliations

Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-4472, USA. jjohnsto@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20672375

Citation

Johnston, Jennifer J., et al. "Molecular Analysis Expands the Spectrum of Phenotypes Associated With GLI3 Mutations." Human Mutation, vol. 31, no. 10, 2010, pp. 1142-54.
Johnston JJ, Sapp JC, Turner JT, et al. Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations. Hum Mutat. 2010;31(10):1142-54.
Johnston, J. J., Sapp, J. C., Turner, J. T., Amor, D., Aftimos, S., Aleck, K. A., Bocian, M., Bodurtha, J. N., Cox, G. F., Curry, C. J., Day, R., Donnai, D., Field, M., Fujiwara, I., Gabbett, M., Gal, M., Graham, J. M., Hedera, P., Hennekam, R. C., ... Biesecker, L. G. (2010). Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations. Human Mutation, 31(10), 1142-54. https://doi.org/10.1002/humu.21328
Johnston JJ, et al. Molecular Analysis Expands the Spectrum of Phenotypes Associated With GLI3 Mutations. Hum Mutat. 2010;31(10):1142-54. PubMed PMID: 20672375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations. AU - Johnston,Jennifer J, AU - Sapp,Julie C, AU - Turner,Joyce T, AU - Amor,David, AU - Aftimos,Salim, AU - Aleck,Kyrieckos A, AU - Bocian,Maureen, AU - Bodurtha,Joann N, AU - Cox,Gerald F, AU - Curry,Cynthia J, AU - Day,Ruth, AU - Donnai,Dian, AU - Field,Michael, AU - Fujiwara,Ikuma, AU - Gabbett,Michael, AU - Gal,Moran, AU - Graham,John M, AU - Hedera,Peter, AU - Hennekam,Raoul C M, AU - Hersh,Joseph H, AU - Hopkin,Robert J, AU - Kayserili,Hülya, AU - Kidd,Alexa M J, AU - Kimonis,Virginia, AU - Lin,Angela E, AU - Lynch,Sally Ann, AU - Maisenbacher,Melissa, AU - Mansour,Sahar, AU - McGaughran,Julie, AU - Mehta,Lakshmi, AU - Murphy,Helen, AU - Raygada,Margarita, AU - Robin,Nathaniel H, AU - Rope,Alan F, AU - Rosenbaum,Kenneth N, AU - Schaefer,G Bradley, AU - Shealy,Amy, AU - Smith,Wendy, AU - Soller,Maria, AU - Sommer,Annmarie, AU - Stalker,Heather J, AU - Steiner,Bernhard, AU - Stephan,Mark J, AU - Tilstra,David, AU - Tomkins,Susan, AU - Trapane,Pamela, AU - Tsai,Anne Chun-Hui, AU - Van Allen,Margot I, AU - Vasudevan,Pradeep C, AU - Zabel,Bernhard, AU - Zunich,Janice, AU - Black,Graeme C M, AU - Biesecker,Leslie G, PY - 2010/7/31/entrez PY - 2010/7/31/pubmed PY - 2011/2/1/medline SP - 1142 EP - 54 JF - Human mutation JO - Hum Mutat VL - 31 IS - 10 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/20672375/Molecular_analysis_expands_the_spectrum_of_phenotypes_associated_with_GLI3_mutations_ L2 - https://doi.org/10.1002/humu.21328 DB - PRIME DP - Unbound Medicine ER -