Expanding the clinical phenotype of FGFR1 internal tandem duplication.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-03-24 Print Date: 2022-02-01 DOI:10.1101/mcs.a006174
Esko A Kautto, Kathleen M Schieffer, Sean McGrath, Anthony R Miller, Maria Elena Hernandez-Gonzalez, Samantha Choi, Miriam R Conces, Esteban Fernandez-Faith, Mai-Lan Ho, Kristy Lee, Anna P Lillis, Gregory D Pearson, Stephen G Kaler, Richard K Wilson, Elaine R Mardis, Vincent Magrini, Jeffrey Leonard, Catherine E Cottrell
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引用次数: 3

Abstract

Closed spinal dysraphism (SD) is a type of neural tube defect originating during early embryonic development whereby the neural tissue of the spinal defect remains covered by skin, often coinciding with markers of cutaneous stigmata. It is hypothesized that these events are caused by multifactorial processes, including genetic and environmental causes. We present an infant with a unique congenital midline lesion associated with a closed SD. Through comprehensive molecular profiling of the intraspinal lesion and contiguous skin lesion, an internal tandem duplication (ITD) of the kinase domain of the fibroblast growth factor receptor 1 (FGFR1) gene was found. This ITD variant is somatic mosaic in nature as supported by a diminished variant allele frequency in the lesional tissue and by its absence in peripheral blood. FGFR1 ITD results in constitutive activation of the receptor tyrosine kinase to promote cell growth, differentiation, and survival through RAS/MAPK signaling. Identification of FGFR1 ITD outside of central nervous system tumors is exceedingly rare, and this report broadens the phenotypic spectrum of somatic mosaic FGFR1-related disease.

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扩大FGFR1内部串联重复的临床表型。
闭合性脊柱发育异常(SD)是一种起源于早期胚胎发育的神经管缺陷,其中脊柱缺陷的神经组织仍然被皮肤覆盖,通常与皮肤斑痕标记相一致。据推测,这些事件是由多因素过程引起的,包括遗传和环境原因。我们提出了一个独特的先天性中线病变与闭合性SD的婴儿。通过对椎管内病变和相邻皮肤病变的综合分子分析,发现成纤维细胞生长因子受体1 (FGFR1)基因激酶结构域的内部串联重复(ITD)。这种ITD变体在本质上是体细胞镶嵌,这是由病变组织中变异等位基因频率减少和外周血中不存在所支持的。FGFR1 ITD导致受体酪氨酸激酶的组成性激活,通过RAS/MAPK信号传导促进细胞生长、分化和存活。在中枢神经系统肿瘤外鉴定FGFR1 ITD极为罕见,该报告拓宽了体细胞马赛克FGFR1相关疾病的表型谱。
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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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