未经证实:STAMBP基因突变,它编码一种叫做STAM结合蛋白的去泛素化异肽酶,与全球发育迟缓有关,小头畸形,毛细血管畸形.由于报告的案件数量有限,STAMBP变异体的功能和表型特征需要进一步阐明.
未经证实:对一名神经发育障碍患者进行全外显子组测序。STAMBP中的新型复合杂合突变[c.843_844del(p。C282Wfs*11)和c.920G>A(p。G307E)]使用Sanger测序进行鉴定和验证。使用3D人类皮质类器官模型来研究STAMBP的功能和新突变的致病性(c.920G>A,p.G307E)。
未经评估:患者出现了整体发育迟缓,自闭症谱系障碍,小头畸形,癫痫,和畸形的面部特征,但皮肤和器官上没有明显的毛细血管畸形。STAMBP敲除(KO)的皮质类器官显示神经干细胞(NSC)的增殖显着降低,导致小头畸形的特征较小的类器官。此外,STAMBP破坏不影响早期皮质类器官的凋亡。重新表达野生型STAMBP后,STAMBPG307E,和STAMBPKO类器官内的STAMBPT313I(一种已知的致病突变),只有STAMBPWT拯救了STAMBP缺乏的类器官的增殖受损,但不是STAMBPG307E和STAMBPT313I。
未经证实:我们的研究结果表明,STAMBP突变的临床表型是高度可变的,不同STAMBP基因突变的患者在症状严重程度上存在差异。此处鉴定的STAMBP错义突变是一种新的致病性突变,会损害人脑发育中神经干细胞的增殖。
UNASSIGNED: Mutations in the
STAMBP gene, which encodes a deubiquitinating isopeptidase called STAM-binding protein, are related to global developmental delay, microcephaly, and capillary malformation. Owing to the limited number of reported cases, the functional and phenotypic characteristics of STAMBP variants require further elucidation.
UNASSIGNED: Whole exome sequencing was performed on a patient presenting with a neurodevelopmental disorder. Novel compound heterozygous mutations in STAMBP [c.843_844del (p.C282Wfs*11) and c.920G > A (p.G307E)] were identified and validated using Sanger sequencing. A 3D human cortical organoid model was used to investigate the function of STAMBP and the pathogenicity of the novel mutation (c.920G > A, p.G307E).
UNASSIGNED: The patient was presented with global developmental delay, autism spectrum disorder, microcephaly, epilepsy, and dysmorphic facial features but without apparent capillary malformation on the skin and organs. Cortical organoids with STAMBP knockout (KO) showed significantly lower proliferation of neural stem cells (NSCs), leading to smaller organoids that are characteristic of microcephaly. Furthermore,
STAMBP disruption did not affect apoptosis in early cortical organoids. After re-expressing wild-type
STAMBP,
STAMBP G307E , and
STAMBP T313I (a known pathogenic mutation) within
STAMBP KO organoids, only
STAMBP WT rescued the impaired proliferation of
STAMBP deficient organoids, but not
STAMBP G307E and
STAMBP T313I .
UNASSIGNED: Our findings demonstrate that the clinical phenotype of STAMBP mutations is highly variable, and patients with different STAMBP mutations show differences in the severity of symptoms. The STAMBP missense mutation identified here is a novel pathogenic mutation that impairs the proliferation of NSCs in human brain development.