GLI2 基因突变患者的临床特征——表型多样性。
Clinical findings in patients with GLI2 mutations--phenotypic variability.
机构信息
Hospital of Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil.
出版信息
Clin Genet. 2012 Jan;81(1):70-5. doi: 10.1111/j.1399-0004.2010.01606.x. Epub 2011 Jan 19.
Abstract
Mutations in the human GLI2 gene were first reported in association with defective anterior pituitary formation, panhypopituitarism, and forebrain anomalies represented by typical holoprosencephaly (HPE) and holoprosencephaly-like (HPE-L) phenotypes and postaxial polydactyly. Subsequently, anophthalmia plus orbital anomalies, heminasal aplasia, branchial arch anomalies and polydactyly have also been incorporated into the general phenotype. Here we described six Brazilian patients with phenotypic manifestations that range from isolated cleft lip/palate with polydactyly, branchial arch anomalies to semi-lobar holoprosencephaly. Novel sequence variants were found in the GLI2 gene in patients with marked involvement of the temporomandibular joint (TMJ), a new clinical finding observed with mutations of this gene. Clinical, molecular and genetic aspects are discussed.
摘要
人类 GLI2 基因突变首先与前脑垂体形成缺陷、全垂体功能减退和前脑异常相关联，表现为典型的无脑回畸形（HPE）和无脑回畸形样（HPE-L）表型以及后轴多指（趾）畸形。随后，无眼症加眼眶异常、半侧鼻发育不全、鳃弓异常和多指（趾）畸形也被纳入一般表型。在这里，我们描述了 6 名巴西患者，他们的表型表现从单纯的唇裂/腭裂伴多指（趾）、鳃弓异常到半侧脑回畸形。在颞下颌关节（TMJ）严重受累的患者中发现了 GLI2 基因的新序列变异，这是该基因突变的一个新的临床发现。讨论了临床、分子和遗传方面的问题。
相似文献
1
Clinical findings in patients with GLI2 mutations--phenotypic variability.GLI2 基因突变患者的临床特征——表型多样性。
Clin Genet. 2012 Jan;81(1):70-5. doi: 10.1111/j.1399-0004.2010.01606.x. Epub 2011 Jan 19.
2
GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum?四名巴西患者中的GLI2突变：表型谱有多广泛？
Am J Med Genet A. 2006 Dec 1;140(23):2571-6. doi: 10.1002/ajmg.a.31370.
3
Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly.GLI2基因的致病性突变会导致一种与前脑无裂畸形不同的特定表型。
J Med Genet. 2014 Jun;51(6):413-8. doi: 10.1136/jmedgenet-2013-102249. Epub 2014 Apr 17.
4
A patient with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3 Mb deletion encompassing GLI2.一名具有轻度全前脑畸形谱系表型和内脏转位的患者，携带一个 1.3Mb 的缺失，该缺失涵盖了 GLI2 基因。
Am J Med Genet A. 2012 Jan;158A(1):166-73. doi: 10.1002/ajmg.a.34350. Epub 2011 Nov 21.
5
A familial GLI2 deletion (2q14.2) not associated with the holoprosencephaly syndrome phenotype.一种与前脑无裂畸形综合征表型无关的家族性GLI2缺失（2q14.2）。
Am J Med Genet A. 2015 May;167A(5):1121-4. doi: 10.1002/ajmg.a.36972. Epub 2015 Mar 28.
6
Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly.在无脑畸形患者中，新型杂合性无义 GLI2 突变与垂体后叶异位而无全前脑。
J Clin Endocrinol Metab. 2010 Nov;95(11):E384-91. doi: 10.1210/jc.2010-1050. Epub 2010 Aug 4.
7
Holoprosencephaly in a family segregating novel variants in ZIC2 and GLI2.家族性无脑回畸形中 ZIC2 和 GLI2 新型变异的分离。
Am J Med Genet A. 2011 Apr;155A(4):860-4. doi: 10.1002/ajmg.a.33903. Epub 2011 Mar 17.
8
Holoprosencephaly-like phenotype: clinical and genetic perspectives.全前脑畸形样表型：临床与遗传学视角
Am J Med Genet A. 2006 Dec 1;140(23):2587-93. doi: 10.1002/ajmg.a.31378.
9
Holoprosencephaly-Polydactyly syndrome: in search of an etiology.前脑无裂畸形-多指（趾）综合征：病因探寻
Eur J Med Genet. 2008 Mar-Apr;51(2):106-12. doi: 10.1016/j.ejmg.2007.08.004. Epub 2007 Sep 15.
10
Holoprosencephaly, ectrodactyly, and bilateral cleft of lip and palate: exclusion of SHH, TGIF, SIX3, GLI2, TP73L, and DHCR7 as candidate genes.前脑无裂畸形、缺指（趾）畸形以及双侧唇腭裂：排除SHH、TGIF、SIX3、GLI2、TP73L和DHCR7作为候选基因。
Am J Med Genet A. 2009 Jun;149A(6):1277-9. doi: 10.1002/ajmg.a.32844.
引用本文的文献
1
Diagnostic yield of trio exome sequencing as a first-tier test for identifying genetic causes of pregnancy loss.三联外显子测序作为识别复发性流产遗传病因的一线检测方法的诊断率
J Hum Genet. 2025 Jul 24. doi: 10.1038/s10038-025-01373-7.
2
A Novel Missense Variant in in Three Children with Multiple Pituitary Hormone Deficiency Belonging to Two Unrelated Families and Contribution of Additional and Variant.两个无关家庭中三名患有多种垂体激素缺乏症儿童的一种新型错义变体以及其他变体的作用
Children (Basel). 2025 Mar 14;12(3):364. doi: 10.3390/children12030364.
3
Management of anophthalmia, microphthalmia and coloboma in the newborn, shared care between neonatologist and ophthalmologist: a literature review.新生儿无眼、小眼和缺损的管理：新生儿科医生与眼科医生的共同照护——文献综述
Ital J Pediatr. 2025 Mar 5;51(1):65. doi: 10.1186/s13052-025-01882-3.
4
Heterozygous missense variant in GLI2 impairs human endocrine pancreas development.GLI2 杂合错义变异会损害人类内分泌胰腺的发育。
Nat Commun. 2024 Mar 20;15(1):2483. doi: 10.1038/s41467-024-46740-8.
5
Exome sequencing improves genetic diagnosis of congenital orofacial clefts.外显子组测序可改善先天性口腔颌面部裂隙的基因诊断。
Front Genet. 2023 Sep 7;14:1252823. doi: 10.3389/fgene.2023.1252823. eCollection 2023.
6
Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management.全前脑畸形：胚胎学、临床表型、病因及管理综述
Children (Basel). 2023 Mar 30;10(4):647. doi: 10.3390/children10040647.
7
Cell fate decisions, transcription factors and signaling during early retinal development.早期视网膜发育过程中的细胞命运决定、转录因子和信号转导。
Prog Retin Eye Res. 2022 Nov;91:101093. doi: 10.1016/j.preteyeres.2022.101093. Epub 2022 Jul 8.
8
Disorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic Findings.《乌克兰大样本队列中性发育障碍的临床多样性和遗传学发现》
Front Endocrinol (Lausanne). 2022 Mar 21;13:810782. doi: 10.3389/fendo.2022.810782. eCollection 2022.
9
The Genetic Backdrop of Hypogonadotropic Hypogonadism.低促性腺激素性性腺功能减退的遗传背景。
Int J Mol Sci. 2021 Dec 8;22(24):13241. doi: 10.3390/ijms222413241.
10
Molecular Bases of Human Malformation Syndromes Involving the SHH Pathway: GLIA/R Balance and Cardinal Phenotypes.涉及 SHH 通路的人类畸形综合征的分子基础：神经胶质/神经元平衡和主要表型。
Int J Mol Sci. 2021 Dec 2;22(23):13060. doi: 10.3390/ijms222313060.
本文引用的文献
1
Clinical characterization of individuals with deletions of genes in holoprosencephaly pathways by aCGH refines the phenotypic spectrum of HPE.通过 aCGH 对全前脑裂畸形通路基因缺失个体进行临床特征分析，可细化 HPE 的表型谱。
Hum Genet. 2010 Apr;127(4):421-40. doi: 10.1007/s00439-009-0778-7.
2
Temporomandibular joint formation requires two distinct hedgehog-dependent steps.颞下颌关节的形成需要两个不同的依赖刺猬信号通路的步骤。
Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18297-302. doi: 10.1073/pnas.0908836106. Epub 2009 Oct 8.
3
EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally.在一例半叶全前脑畸形中间型病例中缺失的EYA4，在物理和功能上均与SIX3相互作用。
Hum Mutat. 2009 Oct;30(10):E946-55. doi: 10.1002/humu.21094.
4
A sonic hedgehog missense mutation associated with holoprosencephaly causes defective binding to GAS1.一种与前脑无裂畸形相关的音猬因子错义突变导致与生长停滞特异性基因1的结合缺陷。
J Biol Chem. 2009 Jul 17;284(29):19169-72. doi: 10.1074/jbc.C109.011957. Epub 2009 May 28.
5
Array-CGH analysis indicates a high prevalence of genomic rearrangements in holoprosencephaly: an updated map of candidate loci.阵列比较基因组杂交分析表明全前脑畸形中基因组重排的高发生率：候选基因座的更新图谱。
Hum Mutat. 2009 Aug;30(8):1175-82. doi: 10.1002/humu.21016.
6
A novel SIX3 mutation segregates with holoprosencephaly in a large family.一种新的SIX3突变在一个大家庭中与全前脑畸形共分离。
Am J Med Genet A. 2009 May;149A(5):919-25. doi: 10.1002/ajmg.a.32813.
7
Characterization of two ectrodactyly-associated translocation breakpoints separated by 2.5 Mb on chromosome 2q14.1-q14.2.2号染色体2q14.1-q14.2上两个相距2.5 Mb的并指畸形相关易位断点的特征分析。
Eur J Hum Genet. 2009 Aug;17(8):1024-33. doi: 10.1038/ejhg.2009.2. Epub 2009 Feb 18.
8
Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans.DISP1的截短型功能丧失突变导致人类出现类似前脑无裂畸形的微小特征。
Hum Genet. 2009 May;125(4):393-400. doi: 10.1007/s00439-009-0628-7. Epub 2009 Jan 31.
9
A SHH-responsive signaling center in the forebrain regulates craniofacial morphogenesis via the facial ectoderm.前脑中的一个SHH反应信号中心通过面部外胚层调节颅面形态发生。
Development. 2009 Jan;136(1):107-16. doi: 10.1242/dev.026583. Epub 2008 Nov 26.
10
Induction of mirror-image supernumerary jaws in chicken mandibular mesenchyme by Sonic Hedgehog-producing cells.通过产生音猬因子的细胞诱导鸡下颌间充质中镜像多余颌骨的形成。
Development. 2008 Jul;135(13):2311-9. doi: 10.1242/dev.019125.
Zotero 插件