LRRC32 基因中存在纯合的移码突变，该基因编码 TGFβ 受体，与腭裂、增殖性视网膜病变和发育迟缓有关。
Homozygous stop-gain variant in LRRC32, encoding a TGFβ receptor, associated with cleft palate, proliferative retinopathy, and developmental delay.
机构信息
Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel.
Medical Genetics Institute, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
出版信息
Eur J Hum Genet. 2019 Aug;27(8):1315-1319. doi: 10.1038/s41431-019-0380-y. Epub 2019 Apr 11.
Abstract
The transforming growth factor-beta (TGFβ) signaling pathway is essential for palatogenesis and retinal development. Glycoprotein A repetitions predominant (GARP), encoded by LRRC32, is a TGFβ cell surface receptor that has been studied primarily in the context of cellular immunity. We identified a homozygous stop-gain variant in LRRC32 (c.1630C>T; p.(Arg544Ter)) in two families with developmental delay, cleft palate, and proliferative retinopathy. Garp-null mice have palate defects and die within 24 h after birth. Our study establishes LRRC32 as a candidate disease-associated gene in humans and lends further support to the role of the TGFβ pathway in palatogenesis and retinal development.
摘要
转化生长因子-β（TGFβ）信号通路对于腭发生和视网膜发育至关重要。LRRC32 编码的糖蛋白 A 重复为主（GARP）是 TGFβ 细胞表面受体，主要在细胞免疫的背景下进行研究。我们在两个具有发育迟缓、腭裂和增殖性视网膜病变的家族中发现了 LRRC32 中的纯合终止变异（c.1630C>T；p.(Arg544Ter))。Garp 基因敲除小鼠有腭裂缺陷，并在出生后 24 小时内死亡。我们的研究将 LRRC32 确立为人类疾病相关基因的候选基因，并进一步支持 TGFβ 途径在腭发生和视网膜发育中的作用。
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本文引用的文献
1
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Front Med. 2018 Aug;12(4):387-411. doi: 10.1007/s11684-018-0646-8. Epub 2018 Jul 24.
2
B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.B 淋巴细胞通过细胞表面 GARP-TGF-β 复合物发挥免疫耐受作用。
JCI Insight. 2018 Apr 5;3(7). doi: 10.1172/jci.insight.99863.
3
Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer.GARP-TGF-β 的免疫调节功能及其在炎症和癌症中的治疗意义。
J Hematol Oncol. 2018 Feb 20;11(1):24. doi: 10.1186/s13045-018-0570-z.
4
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6
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7
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8
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PLoS One. 2016 Apr 7;11(4):e0153290. doi: 10.1371/journal.pone.0153290. eCollection 2016.
9
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Development. 2013 Mar;140(6):1220-30. doi: 10.1242/dev.089615. Epub 2013 Feb 13.
10
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