Goldberg–Shprintzen syndrome (GOSHS) is caused by loss of function variants in the kinesin binding protein gene (KIFBP). However, the phenotypic range of this syndrome is wide, indicating that other factors may play a role. To date, 37 patients with GOSHS have been reported. Here, we document nine new patients with variants in KIFBP: seven with nonsense variants and two with missense variants. To our knowledge, this is the first time that missense variants have been reported in GOSHS. We functionally investigated the effect of the variants identified, in an attempt to find a genotype–phenotype correlation. We also determined whether common Hirschsprung disease (HSCR)‐associated single nucleotide polymorphisms (SNPs), could explain the presence of HSCR in GOSHS. Our results showed that the missense variants led to reduced expression of KIFBP, while the truncating variants resulted in lack of protein. However, no correlation was found between the severity of GOSHS and the location of the variants. We were also unable to find a correlation between common HSCR‐associated SNPs, and HSCR development in GOSHS. In conclusion, we show that reduced, as well as lack of KIFBP expression can lead to GOSHS, and our results suggest that a threshold expression of KIFBP may modulate phenotypic variability of the disease.

中文翻译：

---

Goldberg-Shprintzen 综合征由 KIFBP 的缺失或表达水平降低决定。

Goldberg–Shprintzen 综合征 (GOSHS) 是由驱动蛋白结合蛋白基因 ( KIFBP )中功能变异的丧失引起的。然而，该综合征的表型范围很广，表明其他因素可能起作用。迄今为止，已报告了 37 名 GOSHS 患者。在这里，我们记录了九名具有KIFBP变异的新患者：七个带有无义变体，两个带有错义变体。据我们所知，这是第一次在 GOSHS 中报告错义变异。我们从功能上研究了已识别变体的影响，试图找到基因型 - 表型相关性。我们还确定了普通先天性巨结肠 (HSCR) 相关的单核苷酸多态性 (SNP) 是否可以解释 GOSHS 中 HSCR 的存在。我们的结果表明，错义变体导致 KIFBP 表达降低，而截短变体导致蛋白质缺乏。然而，在 GOSHS 的严重程度和变异的位置之间没有发现相关性。我们也无法找到常见的 HSCR 相关 SNP 与 GOSHS 中 HSCR 发展之间的相关性。总之，我们表明，减少，