人类前脑无裂畸形的基因型-表型相关性分析。
Analysis of genotype-phenotype correlations in human holoprosencephaly.
机构信息
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):133-41. doi: 10.1002/ajmg.c.30240.
Abstract
Since the discovery of the first gene causing holoprosencephaly (HPE), over 500 patients with mutations in genes associated with non-chromosomal, non-syndromic HPE have been described, with detailed descriptions available in over 300. Comprehensive clinical analysis of these individuals allows examination for the presence of genotype-phenotype correlations. These correlations allow a degree of differentiation between patients with mutations in different HPE-associated genes and for the application of functional studies to determine intragenic correlations. These early correlations are an important advance in the understanding of the clinical aspects of this disease, and in general argue for continued analysis of the genetic and clinical findings of large cohorts of patients with rare diseases in order to better inform both basic biological insight and care and counseling for affected patients and families.
摘要
自发现首个导致全前脑畸形（HPE）的基因以来，已有超过 500 名患者被描述为与非染色体、非综合征性 HPE 相关基因突变，其中超过 300 名患者的详细描述可用。对这些个体进行全面的临床分析可检查是否存在基因型-表型相关性。这些相关性允许在不同 HPE 相关基因突变的患者之间进行一定程度的区分，并可应用功能研究来确定基因内相关性。这些早期相关性是理解该疾病临床方面的重要进展，通常主张对患有罕见疾病的大量患者的遗传和临床发现进行持续分析，以便更好地为受影响的患者及其家属提供基本的生物学见解和护理及咨询。
相似文献
1
Analysis of genotype-phenotype correlations in human holoprosencephaly.人类前脑无裂畸形的基因型-表型相关性分析。
Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):133-41. doi: 10.1002/ajmg.c.30240.
2
New findings for phenotype-genotype correlations in a large European series of holoprosencephaly cases.新发现：大型欧洲无脑回畸形病例系列中的表型-基因型相关性。
J Med Genet. 2011 Nov;48(11):752-60. doi: 10.1136/jmedgenet-2011-100339. Epub 2011 Sep 22.
3
Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals.人类前脑无裂畸形中 ZIC2 基因突变：一种新的 ZIC2 特异性表型的描述及对 157 个人的综合分析。
J Med Genet. 2010 Aug;47(8):513-24. doi: 10.1136/jmg.2009.073049. Epub 2009 Dec 2.
4
Comparison of mutation findings in ZIC2 between microform and classical holoprosencephaly in a Brazilian cohort.巴西队列中微脑回型与经典型前脑无裂畸形患者ZIC2基因突变结果的比较。
Birth Defects Res A Clin Mol Teratol. 2012 Nov;94(11):912-7. doi: 10.1002/bdra.23047. Epub 2012 Jul 27.
5
Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations.全前脑谱系特征患者中SHH、ZIC2、SIX3和TGIF基因的分子筛查：突变综述及基因型-表型相关性
Hum Mutat. 2004 Jul;24(1):43-51. doi: 10.1002/humu.20056.
6
Holoprosencephaly and holoprosencephaly-like phenotypes: Review of facial and molecular findings in patients from a craniofacial hospital in Brazil.无脑回畸形和类似无脑回畸形表型：巴西颅面医院患者的面部和分子研究回顾。
Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):149-57. doi: 10.1002/ajmg.c.30247.
7
Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function.全前脑畸形中SIX3相关突变的临床谱：基因型、表型与功能之间的相关性
J Med Genet. 2009 Jun;46(6):389-98. doi: 10.1136/jmg.2008.063818. Epub 2009 Apr 2.
8
Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre- and postnatal diagnostic testing in Germany.进一步证明前脑无裂畸形的复杂遗传模式：来自德国产前和产后诊断检测的经验教训。
Am J Med Genet C Semin Med Genet. 2018 Jun;178(2):198-205. doi: 10.1002/ajmg.c.31625.
9
The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly.全前脑畸形中sonic hedgehog基因的突变谱：SHH突变导致相当一部分常染色体显性全前脑畸形。
Hum Mol Genet. 1999 Dec;8(13):2479-88. doi: 10.1093/hmg/8.13.2479.
10
Molecular evaluation of foetuses with holoprosencephaly shows high incidence of microdeletions in the HPE genes.全前脑胎儿的分子评估显示，HPE基因的微缺失发生率很高。
Hum Genet. 2006 Mar;119(1-2):1-8. doi: 10.1007/s00439-005-0097-6. Epub 2005 Dec 2.
引用本文的文献
1
Exome Sequencing Reveals the Genetic Architecture of Non-syndromic Orofacial Clefts and Identifies BOC as a Novel Causal Gene.外显子组测序揭示非综合征性口面部裂隙的遗传结构并确定BOC为一个新的致病基因。
Adv Sci (Weinh). 2025 Aug;12(32):e12073. doi: 10.1002/advs.202412073. Epub 2025 Jun 4.
2
Semilobar Holoprosencephaly Caused by a Novel and De Novo Pathogenic Variant.一种新的、新发的致病变异导致的半叶型前脑无裂畸形
Balkan J Med Genet. 2023 May 2;25(2):71-76. doi: 10.2478/bjmg-2022-0017. eCollection 2023 May.
3
Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.Frem1 活性在颅神经嵴间质中由 Sonic hedgehog 信号通路调节，该通路在面部正中发育过程中发挥作用。
Dev Dyn. 2023 Apr;252(4):483-494. doi: 10.1002/dvdy.555. Epub 2022 Dec 19.
4
Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.SIX3 和 POU1F1 中的杂合变体导致人和小鼠的垂体激素缺乏。
Hum Mol Genet. 2023 Jan 13;32(3):367-385. doi: 10.1093/hmg/ddac192.
5
Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency: A single center experience from over 30 years.儿童期起病的联合垂体激素缺乏症的临床表现与诊断：30多年的单中心经验
EClinicalMedicine. 2022 Jul 18;51:101556. doi: 10.1016/j.eclinm.2022.101556. eCollection 2022 Sep.
6
Multidisciplinary approach to Gorlin-Goltz syndrome: from diagnosis to surgical treatment of jawbones.戈林-戈尔茨综合征的多学科治疗方法：从诊断到颌骨的外科治疗
Maxillofac Plast Reconstr Surg. 2022 Jul 18;44(1):25. doi: 10.1186/s40902-022-00355-5.
7
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes.《Sonic Hedgehog 在人类前脑无裂畸形和短肋多指（趾）畸形综合征中的作用》
Int J Mol Sci. 2021 Sep 12;22(18):9854. doi: 10.3390/ijms22189854.
8
High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency.高通量剪接分析鉴定了导致垂体激素缺乏的 POU1F1 错义突变和沉默剪接破坏变体。
Am J Hum Genet. 2021 Aug 5;108(8):1526-1539. doi: 10.1016/j.ajhg.2021.06.013. Epub 2021 Jul 15.
9
Diabetes, Oxidative Stress, and DNA Damage Modulate Cranial Neural Crest Cell Development and the Phenotype Variability of Craniofacial Disorders.糖尿病、氧化应激和DNA损伤调节颅神经嵴细胞发育及颅面疾病的表型变异性。
Front Cell Dev Biol. 2021 May 20;9:644410. doi: 10.3389/fcell.2021.644410. eCollection 2021.
10
Variation in phenotypes from a Bmp-Gata3 genetic pathway is modulated by Shh signaling.Bmp-Gata3 遗传途径引起的表型变化受 Shh 信号的调节。
PLoS Genet. 2021 May 25;17(5):e1009579. doi: 10.1371/journal.pgen.1009579. eCollection 2021 May.
本文引用的文献
1
Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals.人类前脑无裂畸形中 ZIC2 基因突变：一种新的 ZIC2 特异性表型的描述及对 157 个人的综合分析。
J Med Genet. 2010 Aug;47(8):513-24. doi: 10.1136/jmg.2009.073049. Epub 2009 Dec 2.
2
The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis.人类中SHH基因内全前脑畸形相关变化的突变谱预示着通过配体的关键结构改变或其合成改变导致功能丧失。
Hum Mutat. 2009 Oct;30(10):E921-35. doi: 10.1002/humu.21090.
3
Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly.NODAL 突变和修饰因子的累积配体活性与人类心脏缺陷和全前脑畸形有关。
Mol Genet Metab. 2009 Sep-Oct;98(1-2):225-34. doi: 10.1016/j.ymgme.2009.05.005. Epub 2009 May 27.
4
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.
5
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.
6
Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function.全前脑畸形中SIX3相关突变的临床谱：基因型、表型与功能之间的相关性
J Med Genet. 2009 Jun;46(6):389-98. doi: 10.1136/jmg.2008.063818. Epub 2009 Apr 2.
7
Murine models of holoprosencephaly.全前脑畸形的小鼠模型。
Curr Top Dev Biol. 2008;84:139-70. doi: 10.1016/S0070-2153(08)00603-0.
8
Disorders of prosencephalic development.前脑发育障碍。
Prenat Diagn. 2009 Apr;29(4):340-54. doi: 10.1002/pd.2208.
9
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.
10
The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism.人类ZIC2基因内全谱前脑无裂畸形相关突变预示功能丧失是主要疾病机制。
Hum Mutat. 2009 Apr;30(4):E541-54. doi: 10.1002/humu.20982.
Zotero 插件