PDF(Pubmed)
Abstract：
Truncating variants in specific exons of Fibrosin-like protein 1 (FBRSL1) were recently reported to cause a novel malformation and intellectual disability syndrome. The clinical spectrum includes microcephaly, facial dysmorphism, cleft palate, skin creases, skeletal anomalies and contractures, postnatal growth retardation, global developmental delay as well as respiratory problems, hearing impairment and heart defects. The function of FBRSL1 is largely unknown, but pathogenic variants in the FBRSL1 paralog Autism Susceptibility Candidate 2 (AUTS2) are causative for an intellectual disability syndrome with microcephaly (AUTS2 syndrome). Some patients with AUTS2 syndrome also show additional symptoms like heart defects and contractures overlapping with the phenotype presented by patients with FBRSL1 mutations. For AUTS2, a dual function, depending on different isoforms, was described and suggested for FBRSL1. Both, nuclear FBRSL1 and AUTS2 are components of the Polycomb subcomplexes PRC1.3 and PRC1.5. These complexes have essential roles in developmental processes, cellular differentiation and proliferation by regulating gene expression via histone modification. In addition, cytoplasmic AUTS2 controls neural development, neuronal migration and neurite extension by regulating the cytoskeleton. Here, we review recent data on FBRSL1 in respect to previously published data on AUTS2 to gain further insights into its molecular function, its role in development as well as its impact on human genetics.
摘要：
最近有报道称，纤维蛋白酶样蛋白1（FBRSL1）特定外显子中的截短变体会导致一种新的畸形和智力障碍综合征。临床频谱包括小头畸形，面部畸形,腭裂,皮肤皱纹，骨骼异常和挛缩，出生后生长迟缓，全球发育迟缓以及呼吸问题，听力障碍和心脏缺陷。FBRSL1的功能在很大程度上是未知的，但是FBRSL1旁系物孤独症易感性候选2(AUTS2)中的致病变异是伴有小头症的智力障碍综合征(AUTS2综合征)的病因.一些AUTS2综合征患者还表现出其他症状，如心脏缺陷和挛缩，与FBRSL1突变患者的表型重叠。对于AUTS2，双重功能，根据不同的同工型，对FBRSL1进行了描述和建议。两者,核FBRSL1和AUTS2是Polycomb亚复合物PRC1.3和PRC1.5的组分。这些复合物在发育过程中具有重要作用，细胞分化和增殖通过组蛋白修饰调节基因表达。此外,细胞质AUTS2控制神经发育，神经元迁移和神经突延伸通过调节细胞骨架。这里,我们回顾了关于FBRSL1的最新数据，以进一步了解其分子功能，它在发展中的作用以及对人类遗传学的影响。
