粘附蛋白复合物是一种多亚基蛋白复合物,可在细胞分裂过程中调节姐妹染色单体的内聚和分离。此外,这种进化上保守的蛋白质复合物在DNA复制中起着不可或缺的作用,DNA修复,和转录的调节。核心复合物由四个亚基组成:RAD21,SMC1A,SMC3和STAG1/2。这些蛋白质的突变与人类发育障碍有关,统称为“相干体病”。\"
使用临床外显子组测序,我们之前已经确定了3例女性病例,其具有杂合的STAG2突变和重叠的综合征表型.随后,在五名男性家庭成员中发现了一个家族错义变异。
我们现在介绍一个4岁男性发育迟缓的案例,未能茁壮成长,身材矮小,多指有可能致病的STAG2从头错义半合子变异体,c.3027A>T,p.Lys1009Asn.此外,我们将之前报道的4种STAG2变异体的表型与我们的病例进行了比较.
我们得出的结论是,STAG2中的突变会导致一系列新的与性别相关的表型,此外,对神经发育至关重要,人类成长,和行为发展。
The cohesin complex is a multi-subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed \"cohesinopathies.\"
Using clinical exome sequencing, we have previously identified three female cases with heterozygous STAG2 mutations and overlapping syndromic phenotypes. Subsequently, a familial missense variant was identified in five male family members.
We now present the case of a 4-year-old male with developmental delay, failure to thrive, short stature, and polydactyly with a likely pathogenic STAG2 de novo missense hemizygous variant, c.3027A>T, p.Lys1009Asn. Furthermore, we compare the phenotypes of the four previously reported STAG2 variants with our case.
We conclude that mutations in STAG2 cause a novel constellation of sex-specific cohesinopathy-related phenotypes and are furthermore, essential for neurodevelopment, human growth, and behavioral development.