The DONSON gene encodes the downstream neighbor of SON, a replisome component that stabilizes the replication fork during replication. A severe form of microcephalic dwarfism, microcephaly-micromelia syndrome (MIMIS), has been recently associated with DONSON biallelic loss of function. Affected fetuses suffer severe growth restriction, microcephaly, and variable limb malformations which result in intrauterine or perinatal death. All described fetuses carried a homozygous founder mutation (c.1047-9A>G), a splice-altering variant that leads to transcript degradation. We evaluated 2 newborns from a consanguineous Emirati family with severe microcephaly, micromelia, craniofacial dysmorphism, and skeletal abnormalities; both died shortly after birth. Here, we report the second homozygous loss-of-function variant (c.763C>T) in DONSON causing MIMIS, and we provide detailed clinical description of this very rare disorder. In addition, we review all MIMIS cases in the literature and summarize the striking features of this phenotype. This manuscript is aimed to increase the clinical understanding of this rare, extremely severe disorder and encourage clinical and molecular geneticists to consider screening for DONSON loss-of-function variants in families with recurrent pregnancy loss and/or perinatal deaths.

中文翻译：

---

DONSON中与功能丧失型变体相关的小头畸形综合征的进一步描述。

DONSON基因编码SON的下游邻居，SON是复制过程中稳定复制叉的复制体成分。最近，严重形式的小头畸形，小头畸形综合症（MIMIS）与DONSON双等位基因功能丧失有关。受影响的胎儿患有严重的生长受限，小头畸形和肢体畸形，导致子宫内或围产期死亡。所有描述的胎儿均携带纯合的建立者突变（c.1047-9A> G），这是一种剪接改变变体，导致转录物降解。我们评估了来自一个近亲阿联酋家庭的两个新生儿，他们患有严重的小头畸形，小黑点，颅面畸形和骨骼异常。都在出生后不久死亡。在这里，我们报告了导致MIMIS的DONSON中的第二个纯合功能缺失变体（c.763C> T），并且我们提供了这种非常罕见的疾病的详细临床描述。此外，我们回顾了文献中所有MIMIS病例并总结了该表型的显着特征。该手稿旨在增加对该罕见，极为严重的疾病的临床理解，并鼓励临床和分子遗传学家考虑对经常性流产和/或围产期死亡的家庭筛查DONSON功能丧失的变异体。