Abstract：
DICER1 tumor predisposition syndrome is a pleiotropic disorder that gives rise to various mainly pediatric-onset lesions. We report an extraskeletal chondroma (EC) of the great toe occurring in a child who, unusually, carries a germline \"hotspot\" missense DICER1 variant rather than the more usual loss-of-function (LOF) variant. No heterozygous LOF allele was identified in the EC. We demonstrate this variant impairs 5p cleavage of precursor-miRNA (pre-miRNA) and competes with wild-type (WT) DICER1 protein for pre-miRNA processing. These results suggest a mechanism through which a germline RNase IIIb variant could impair pre-miRNA processing without complete LOF of the WT DICER1 allele.
摘要：
DICER1肿瘤易感性综合征是一种多效性疾病，可引起各种主要是儿科发作的病变。我们报告了一个大脚趾的骨外软骨瘤（EC）发生在一个孩子身上，不寻常的,携带种系“热点”错义DICER1变体，而不是更常见的功能丧失(LOF)变体。在EC中未鉴定出杂合LOF等位基因。我们证明了这种变体损害前体miRNA（pre-miRNA）的5p切割，并与野生型（WT）DICER1蛋白竞争pre-miRNA加工。这些结果表明一种机制,通过该机制,种系RNA酶IIIb变体可以在没有WTDICER1等位基因的完全LOF的情况下损害pre-miRNA加工。
