Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations

被引：90

作者：

Johnston, Jennifer J. ^{[1
]}

Sapp, Julie C. ^{[1
]}

Turner, Joyce T. ^{[1
]}

Amor, David ^{[2
]}

Aftimos, Salim ^{[3
]}

Aleck, Kyrieckos A. ^{[4
]}

Bocian, Maureen ^{[5
]}

Bodurtha, Joann N. ^{[6
]}

Cox, Gerald F. ^{[7
,8
,9
]}

Curry, Cynthia J. ^{[10
]}

Day, Ruth ^{[11
]}

Donnai, Dian ^{[12
]}

Field, Michael ^{[13
]}

Fujiwara, Ikuma ^{[14
]}

Gabbett, Michael ^{[15
,16
]}

Gal, Moran ^{[17
]}

Graham, John M., Jr. ^{[18
]}

Hedera, Peter ^{[19
]}

Hennekam, Raoul C. M. ^{[20
]}

Hersh, Joseph H. ^{[21
]}

Hopkin, Robert J. ^{[22
]}

Kayserili, Hulya ^{[23
]}

Kidd, Alexa M. J. ^{[24
]}

Kimonis, Virginia ^{[5
]}

Lin, Angela E. ^{[25
]}

Lynch, Sally Ann ^{[26
]}

Maisenbacher, Melissa ^{[27
]}

Mansour, Sahar ^{[28
]}

McGaughran, Julie ^{[15
,16
]}

Mehta, Lakshmi ^{[29
]}

Murphy, Helen ^{[12
]}

Raygada, Margarita ^{[30
]}

Robin, Nathaniel H. ^{[31
]}

Rope, Alan F. ^{[32
]}

Rosenbaum, Kenneth N. ^{[33
]}

Schaefer, G. Bradley ^{[34
]}

Shealy, Amy ^{[35
]}

Smith, Wendy ^{[36
]}

Soller, Maria ^{[37
]}

Sommer, Annmarie ^{[38
,39
]}

Stalker, Heather J. ^{[27
]}

Steiner, Bernhard ^{[40
]}

Stephan, Mark J. ^{[41
]}

Tilstra, David ^{[42
]}

Tomkins, Susan ^{[43
]}

Trapane, Pamela ^{[44
]}

Tsai, Anne Chun-Hui ^{[45
]}

Van Allen, Margot I. ^{[46
]}

Vasudevan, Pradeep C. ^{[47
]}

Zabel, Bernhard ^{[48
]}

机构：

[1] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA

[2] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia

[3] Auckland City Hosp, No Reg Genet Serv, Auckland, New Zealand

[4] St Josephs Hosp, Phoenix, AZ USA

[5] Univ Calif Irvine, Dept Pediat, Med Ctr, Div Genet & Metab, Orange, CA 92668 USA

[6] Virginia Commonwealth Univ, Dept Human & Mol Genet Pediat Obstet Gynecol Epid, Richmond, VA USA

[7] Harvard Univ, Sch Med, Div Genet, Boston, MA USA

[8] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[9] Genzyme Corp, Clin Res, Cambridge, MA USA

[10] Genet Med Cent Calif Univ Calif, San Francisco, CA USA

[11] Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England

[12] Univ Manchester, Manchester Acad Heath Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England

[13] Nepean Hosp, Dept Clin Genet, Penrith, NSW, Australia

[14] Tohoku Univ Sch Med, Tohoku Univ Hosp, Dept Pediat, Sendai, Miyagi, Japan

[15] Univ Queensland, Sch Med, Brisbane, Qld, Australia

[16] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia

[17] Shaare Zedek Med Ctr, Inst Med Genet, Jerusalem, Israel

[18] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Med Genet Inst,Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA

[19] Vanderbilt Univ, Dept Neurol, Nashville, TN USA

[20] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Meibergdreef, Az Amsterdam, Netherlands

[21] Univ Louisville, Sch Med, Dept Pediat, Louisville, KY 40292 USA

[22] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA

[23] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, Istanbul, Turkey

[24] Canterbury Hlth Labs, Christchurch, New Zealand

[25] Massachusetts Gen Hosp, Boston, MA 02114 USA

[26] Our Ladys Childrens Hosp, Natl Ctr Med Genet, Dublin 12, Ireland

[27] Univ Florida, Dept Pediat, Div Genet & Metab, Gainesville, FL USA

[28] Univ London, SW Thames Reg Genet Serv, London, England

[29] Mt Sinai Sch Med, Dept Genet & Genom Sci, Div Med Genet, New York, NY USA

[30] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA

[31] Univ Alabama, Dept Genet & Pediat, Birmingham, AL USA

[32] Univ Utah Sch Med, Div Med Genet, Salt Like City, UT USA

[33] Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA

[34] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Genet & Pediat, Sect Genet & Metab,Dept Pediat, Little Rock, AR 72205 USA

[35] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA

[36] Barbara Bush Childrens Hosp Maine Med Ctr, Portland, ME USA

[37] Univ Lund Hosp, Div Clin Genet, Univ & Reg Labs Reg Skane, S-22185 Lund, Sweden

[38] Ohio State Univ Coll Med, Dept Pediat, Columbus, OH USA

[39] Nationwide Childrens Hosp, Columbus, OH USA

[40] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland

[41] Madigan Army Med Ctr, Dept Pediat, Tacoma, WA 98431 USA

[42] CentraCare Clin, Dept Pediat, St Cloud, MN USA

[43] Univ Hosp Bristol, Bristol, Avon, England

[44] Univ Iowa Hosp & Clin, Dept Pediat, Iowa City, IA 52242 USA

[45] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA

[46] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[47] Univ Leicester, Univ Hosp Leicester NHS Trust, Leicester, Leics, England

[48] Univ Hosp Freiburg, Dept Pediat, Freiburg, Germany

[49] Indiana Univ Sch Med NW, Genet Ctr, Gary, IN USA

来源：

HUMAN MUTATION | 2010年 / 31卷 / 10期

基金：

美国国家卫生研究院;

关键词：

GLI3; Greig syndrome; Pallister-Hall syndrome; oral-facial-digital syndrome; PALLISTER-HALL-SYNDROME; FACIAL-DIGITAL SYNDROME; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; MORPHOLOGY STANDARD TERMINOLOGY; POLYDACTYLY TYPE-IV; SYNDROME TYPE-VI; HYPOTHALAMIC HAMARTOMA; ACROCALLOSAL SYNDROME; GENE; PATIENT;

D O I：

10.1002/humu.21328

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1142 / 1154

页数：13

共 38 条

[1] Elements of Morphology: Standard Terminology for the Hands and Feet
Biesecker, Leslie G.
Aase, Jon M.
Clercuzio, Carol
Gurrieri, Fiorella
Temple, I. Karen
Toriello, Helga
[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2009, 149A (01) : 93 - 127
[2] Biesecker LG, 1996, AM J MED GENET, V65, P76, DOI 10.1002/(SICI)1096-8628(19961002)65:1<76::AID-AJMG12>3.0.CO
[3] 2-O
[4] BIESECKER LG, 2001, GENEREVIEWS GENETEST
[5] Complex balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) and two microdeletions del(1)(p31.1p31.1) and del(7)(p14.1p14.1) in a patient with features of Greig cephalopolysyndactyly and mental retardation
Borg, Katarzyna
Nowakowska, Beata
Obersztyn, Ewa
Cheung, Sau Wai
Brycz-Witkowska, Joanna
Korniszewski, Lech
Mazurczak, Tadeusz
Stankiewicz, Pawelt
Bocian, Ewa
[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2007, 143A (22) : 2738 - 2743
[6] Variable phenotype in Greig cephalopolysyndactyly syndrome:: Clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations
Debeer, P
Peeters, H
Driess, S
De Smet, L
Freese, K
Matthijs, G
Bornholdt, D
Devriendt, K
Grzeschik, KH
Fryns, JP
Kalff-Suske, M
[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2003, 120A (01) : 49 - 58
[7] De novo GL13 mutation in acrocallosal syndrome:: broadening the phenotypic spectrum of GL13 defects and overlap with murine models
Elson, E
Perveen, R
Donnai, D
Wall, S
Black, GCM
[J]. JOURNAL OF MEDICAL GENETICS, 2002, 39 (11) : 804 - 806
[8] Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification
Ferrante, MI
Zullo, A
Barra, A
Bimonte, S
Messaddeq, N
Studer, M
Dollé, P
Franco, B
[J]. NATURE GENETICS, 2006, 38 (01) : 112 - 117
[9] Identification of the gene for oral-facial-digital type I syndrome
Ferrante, MI
Giorgio, G
Feather, SA
Bulfone, A
Wright, V
Ghiani, M
Selicorni, A
Gammaro, L
Scolari, F
Woolf, AS
Sylvie, O
Bernard, LM
Malcolm, S
Winter, R
Ballabio, A
Franco, B
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (03) : 569 - 576
[10] Molecular analysis of non-syndromic preaxial polydactyly: preaxial polydactyly type-IV and preaxial polydactyly type-I
Fujioka, H
Ariga, T
Horiuchi, K
Otsu, M
Igawa, H
Kawashima, K
Yamamoto, Y
Sugihara, T
Sakiyama, Y
[J]. CLINICAL GENETICS, 2005, 67 (05) : 429 - 433

← 1 2 3 4 →