Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations.
Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations.
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DOI：
10.1002/humu.21328
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发表时间：
2010-10
期刊：
影响因子：
3.9
通讯作者：
Biesecker, Leslie G.
中科院分区：
文献类型：
--
作者：
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., Jr.;Hedera, Peter;Hennekam, Raoul C. M.;Hersh, Joseph H.;Hopkin, Robert J.;Kayserili, Hulya;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 Chun-Hui;Van Allen, Margot I.;Vasudevan, Pradeep C.;Zabel, Bernhard;Zunich, Janice;Black, Graeme C. M.;Biesecker, Leslie G.
一系列表型包括Greig头多并指（趾）和Pallister-Hall综合征（GCPS，PHS）是由GLI 3基因的致病突变引起的。为了表征GLI 3突变的临床变异性，我们提出了一个由174名先证者组成的队列的子集，用于GLI 3分析。81例具有典型GCPS或PHS的先证者以前曾被报道过，我们在此报告其余93例先证者。这包括19名符合GCPS或PHS临床标准的先证者（12个突变），48名具有GCPS或PHS特征但不符合临床标准（亚GCPS和亚PHS）的先证者（16个突变），21名具有PHS或GCPS和口面指综合征特征的先证者（6个突变）和5名非综合征性多指（趾）先证者（1个突变）。这些数据支持以前确定的基因型-表型相关性，并证明了比以前认识到的更可变的严重程度。在具有口面指综合征特征的患者中发现GLI 3突变支持了GLI 3与纤毛相互作用的观察结果。我们得出结论，GLI 3突变的表型谱比临床诊断标准所涵盖的范围更广，但表型-基因型相关性仍然存在。具有GCPS或PHS特征的个体应筛查GLI 3突变，即使他们不符合临床标准。
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 ninety-three probands here. This includes nineteen probands (twelve mutations) who fulfilled clinical criteria for GCPS or PHS, forty-eight probands (sixteen mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), twenty-one probands (six mutations) with features of PHS or GCPS and oral-facial-digital syndrome and five probands (one mutation) with non-syndromic 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 phenotype-genotype 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.
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影响因子：
2
作者：
Biesecker, Leslie G.;Aase, Jon M.;Clercuzio, Carol;Gurrieri, Fiorella;Temple, I. Karen;Toriello, Helga
通讯作者：
Toriello, Helga
影响因子：
2
作者：
Gurrieri, Fiorella;Franco, Brunella;Neri, Giovanni
通讯作者：
Neri, Giovanni
影响因子：
30.8
作者：
Kang, S;Graham, JM;Biesecker, LG
通讯作者：
Biesecker, LG
DOI：
10.1002/ajmg.1320410436
发表时间：
1991-12-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
MUENKE, M;RUCHELLI, ED;ZACKAI, EH
通讯作者：
ZACKAI, EH
影响因子：
2
作者：
Ng, D;Johnston, JJ;Biesecker, LG
通讯作者：
Biesecker, LG