Fibroblast growth factor receptor‐like 1 (FGFRL1) encodes a transmembrane protein that is related to fibroblast growth factor receptors but lacks an intercellular tyrosine kinase domain. in vitro studies suggest that FGFRL1 inhibits cell proliferation and promotes cell differentiation and cell adhesion. Mice that lack FGFRL1 die shortly after birth from respiratory distress and have abnormally thin diaphragms whose muscular hypoplasia allows the liver to protrude into the thoracic cavity. Haploinsufficiency of FGFRL1 has been hypothesized to contribute to the development of congenital diaphragmatic hernia (CDH) associated with Wolf‐Hirschhorn syndrome. However, data from both humans and mice suggest that disruption of one copy of FGFRL1 alone is insufficient to cause diaphragm defects. Here we report a female fetus with CDH whose 4p16.3 deletion allows us to refine the Wolf‐Hirschhorn syndrome CDH critical region to an approximately 1.9 Mb region that contains FGFRL1. We also report a male infant with isolated left‐sided diaphragm agenesis who carried compound heterozygous missense variants in FGFRL1. These cases provide additional evidence that deleterious FGFRL1 variants may contribute to the development of CDH in humans.

中文翻译：

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FGFRL1 有助于人类先天性膈疝发展的证据

成纤维细胞生长因子受体样 1 ( FGFRL1 ) 编码一种与成纤维细胞生长因子受体相关但缺乏细胞间酪氨酸激酶结构域的跨膜蛋白。体外研究表明，FGFRL1 抑制细胞增殖并促进细胞分化和细胞粘附。缺乏 FGFRL1 的小鼠在出生后不久死于呼吸窘迫，并且具有异常薄的隔膜，其肌肉发育不全使肝脏突出到胸腔中。已经假设FGFRL1 的单倍体不足有助于与 Wolf-Hirschhorn 综合征相关的先天性膈疝 (CDH) 的发展。然而，来自人类和小鼠的数据表明，一个FGFRL1拷贝的破坏单独不足以导致隔膜缺陷。在这里，我们报告了一个患有 CDH 的女性胎儿，其 4p16.3 缺失使我们能够将 Wolf-Hirschhorn 综合征 CDH 关键区域细化为包含FGFRL1的大约 1.9 Mb 区域。我们还报告了一名患有孤立性左侧膈肌发育不全的男婴，他在FGFRL1中携带复合杂合错义变异。这些病例提供了额外的证据，表明有害的FGFRL1变体可能有助于人类 CDH 的发展。