Horm Res Paediatr. 2017;88(3-4):194-200. doi: 10.1159/000477441. Epub 2017 Jul 3.
Mutations in the imprinted gene MKRN3 have been described as a common genetic cause of idiopathic central precocious puberty (CPP), in particular in familial cases. However, the exact prevalence of mutations is unknown. Single nucleotide polymorphisms in 2 other imprinted genes, DLK1 and KCNK9, have been associated with age at menarche. We investigated the prevalence of mutations in MKRN3, DLK1, and KCNK9 genes in a cohort of girls with idiopathic CPP.
MKRN3, DLK1, and KCNK9 coding regions were sequenced in 60 girls with idiopathic CPP (familial in 23 cases).
Three mutations, including a new one, in MKRN3 were found in 2 familial cases (c.1229G>A; p.Cys410Ter and c.477_485del; p.Pro160Cysfs*14) (8.7%) and in 1 sporadic case (c.982C>T; p.Arg328Cys) (2.8%). We did not find rare variants in DLK1 and KCNK9 genes.
(1) The prevalence of MKRN3 mutations in our cohort was similar to that reported in the literature in sporadic cases but lower than previously described in familial ones. This could be due to different inheritance patterns of families studied; (2) we expanded the phenotype of MKRN3 defects describing 3 more patients with MKRN3 mutations; and (3) point mutations in DLK1 and KCNK9 at least do not seem to be a common cause of CPP in girls.
MKRN3 印记基因的突变已被描述为特发性中枢性性早熟（CPP）的常见遗传原因，尤其是在家族性病例中。然而，确切的突变率尚不清楚。另外 2 个印记基因 DLK1 和 KCNK9 的单核苷酸多态性与初潮年龄有关。我们调查了 MKRN3、DLK1 和 KCNK9 基因在特发性 CPP 女孩队列中的突变发生率。
对 60 例特发性 CPP 女孩（23 例为家族性）的 MKRN3、DLK1 和 KCNK9 编码区进行测序。
在 2 个家族性病例（c.1229G>A；p.Cys410Ter 和 c.477_485del；p.Pro160Cysfs*14）（8.7%）和 1 个散发性病例（c.982C>T；p.Arg328Cys）（2.8%）中发现了 3 种突变，包括一种新突变MKRN3。我们未在 DLK1 和 KCNK9 基因中发现罕见变异。
（1）我们队列中 MKRN3 突变的发生率与文献中散发性病例报道的发生率相似，但低于先前描述的家族性病例。这可能是由于研究的家族遗传模式不同；（2）我们通过描述另外 3 名 MKRN3 突变患者，扩展了 MKRN3 缺陷的表型；（3）DLK1 和 KCNK9 的点突变至少似乎不是女孩 CPP 的常见原因。
