Supplementary Material for: A novel truncating variant in Sandestig-Stefanova syndrome with Hydrocephalus

Introduction: Sandestig-Stefanova Syndrome (MIM:#618804) is characterized by pre- and postnatal microcephaly, trigonocephaly, bilateral congenital cataracts, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, periventricular white matter loss, thin corpus callosum, and delayed myelination. Bi-allelic loss-of-function variants in the Nucleoporin 188 (NUP188) (MIM:#615587) gene are implicated in the etiology. Case presentation: Our patient, born to consanguineous parents, presented with tetralogy of Fallot, bilateral congenital cataracts, hydrocephalus, a bifid uvula, a right pelvic kidney, hepatomegaly, facial feature findings, and a history of a similarly affected ex-sibling. Whole exome sequence analysis in the index case revealed a novel homozygous variant NM_015354.2: c.124C>T (p.Arg42Ter) in the NUP188 gene. Conclusion: This study describes a new patient with Sandestig-Stefanova Syndrome harboring a novel pathogenic variant in the NUP188 gene.

引言：桑德斯蒂格-斯特凡诺娃综合征（MIM:#618804）以产前及产后小头畸形、三角头畸形、双侧先天性白内障、小眼球症、唇腭裂或高腭弓、屈曲指、摇椅底足、心脏异常、脑室周围白质减少、胼胝体变薄及髓鞘形成延迟为特征。核孔蛋白188（Nucleoporin 188, NUP188，MIM:#615587）基因的双等位基因功能丧失变异与该病的发病机制相关。

病例报告：本研究的患者来自近亲婚配家庭，表现为法洛四联症、双侧先天性白内障、脑积水、悬雍垂裂、右侧盆腔肾、肝大及面部特征异常，且其同胞曾患同款疾病并已故。对该先证者的全外显子组测序分析显示，其NUP188基因存在新型纯合变异NM_015354.2: c.124C>T（p.Arg42Ter）。

结论：本研究报道了1例携带NUP188基因新型致病变异的桑德斯蒂格-斯特凡诺娃综合征新病例。