Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12‐65K protein, a component of the minor spliceosome. The minor spliceosome plays a role in the splicing of minor (U12‐type) introns, which are present in ~700–800 genes in humans and represent about 0.35% of all introns. Here, we report a second family with biallelic RNPC3 variants in three siblings with a growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. These cases further confirm the association between biallelic RNPC3 variants and severe postnatal growth retardation due to growth hormone deficiency. Furthermore, these cases show that the phenotype of this minor spliceosome‐related disease might be broader than previously described.

中文翻译：

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扩大与生长激素缺乏症相关的双等位基因RNPC3变体的表型。

次要剪接体组分中的致病变异与几种人类疾病有关。最近，据报道，双等位基因RNPC3变体导致严重的孤立的生长激素缺乏和垂体发育不全。该RNPC3的U11 / U12-65K蛋白基因编码，小剪接体的组分。较小的剪接体在较小的（U12型）内含子的剪接中起作用，这些内含子存在于人类的约700-800个基因中，约占所有内含子的0.35％。在这里，我们报告第二个双等位基因RNPC3家族有生长激素缺乏症，中枢性先天性甲状腺功能减退症，先天性白内障，发育延迟/智力缺陷和青春期延迟的三个兄弟姐妹的变异。这些病例进一步证实了双等位基因RNPC3变体与由于生长激素缺乏引起的严重的出生后发育迟缓之间的关联。此外，这些病例表明，这种轻度剪接体相关疾病的表型可能比以前描述的更广泛。