苏氨酸天冬氨酸酶1(Taspase1)是一种高度保守的位点特异性蛋白酶,其底物是控制多种生物学程序的广泛作用的核转录因子。如器官发生,肿瘤发生,和肿瘤进展。迄今为止,在人类疾病中没有涉及Taspase1的单碱基对突变。
确定了一名具有新的诊断异常模式的女婴,包括严重的颅面畸形,前段和后段发育不全,免疫缺陷,和大细胞性贫血.进行基于三重奏的全外显子组测序以鉴定致病变体。
全外显子组测序显示正常女性核型(46,XX),纯合性区域没有增加。先证者对于从头错义变体是杂合的,c.1027G>A预测p.(Val343Met),在TASP1基因(NM_017714.2)中。该变体尚未在群体数据库中观察到,并且预计是有害的。
先前已经报道了一名人类患者具有大的TASP1缺失,并且存在关于几种已知的Taspase1底物在人类颅面和造血障碍中的作用的大量证据。此外,小鼠中的Taspase1缺乏导致颅面,眼科和结构性脑缺陷。一起来看,有大量证据可以得出结论,TASP1变体,p.(Val343Met),对这个病人有致病性.
Threonine Aspartase 1 (Taspase 1) is a highly conserved site-specific protease whose substrates are broad-acting nuclear transcription factors that govern diverse biological programs, such as organogenesis, oncogenesis, and tumor progression. To date, no single base pair mutations in Taspase 1 have been implicated in human disease.
A female infant with a new pattern of diagnostic abnormalities was identified, including severe craniofacial anomalies, anterior and posterior segment dysgenesis, immunodeficiency, and macrocytic anemia. Trio-based whole exome sequencing was performed to identify disease-causing variants.
Whole exome sequencing revealed a normal female karyotype (46,XX) without increased regions of homozygosity. The proband was heterozygous for a de novo missense variant, c.1027G>A predicting p.(Val343Met), in the TASP1 gene (NM_017714.2). This variant has not been observed in population databases and is predicted to be deleterious.
One human patient has been reported previously with a large TASP1 deletion and substantial evidence exists regarding the role of several known Taspase 1 substrates in human craniofacial and hematopoietic disorders. Moreover, Taspase 1 deficiency in mice results in craniofacial, ophthalmological and structural brain defects. Taken together, there exists substantial evidence to conclude that the TASP1 variant, p.(Val343Met), is pathogenic in this patient.