TDGF1的CFC结构域中的功能丧失突变与人类前脑缺陷相关。

A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects.

作者信息

de la Cruz June M, Bamford Richard N, Burdine Rebecca D, Roessler Erich, Barkovich A James, Donnai Dian, Schier Alexander F, Muenke Maximilian

机构信息

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1852, Building 10 Room 10C103, Bethesda, MD 20892-1852, USA.

出版信息

Hum Genet. 2002 May;110(5):422-8. doi: 10.1007/s00439-002-0709-3. Epub 2002 Apr 10.

DOI:10.1007/s00439-002-0709-3

PMID:12073012

Abstract

TDGF1 (CRIPTO) is an EGF-CFC family member and an obligate co-receptor involved in NODAL signaling, a developmental program implicated in midline, forebrain, and left-right axis development in model organisms. Previous studies of CFC1 (CRYPTIC), another member of the EGF-CFC family, demonstrated that normal function of this protein is required for proper laterality development in humans. Here we identify a mutation in the conserved CFC domain of TDGF1 in a patient with midline anomalies of the forebrain. The mutant protein is inactive in a zebrafish rescue assay, indicating a role for TDGF1 in human midline and forebrain development.

摘要

TDGF1（CRIPTO）是表皮生长因子 - CFC（EGF - CFC）家族成员，是参与NODAL信号传导的必需共受体，该信号传导程序与模式生物的中线、前脑和左右轴发育有关。先前对EGF - CFC家族的另一个成员CFC1（CRYPTIC）的研究表明，该蛋白的正常功能是人类正常左右不对称发育所必需的。在此，我们在一名患有前脑中线异常的患者中鉴定出TDGF1保守CFC结构域中的一个突变。该突变蛋白在斑马鱼拯救试验中无活性，表明TDGF1在人类中线和前脑发育中起作用。