Ming J E, Muenke M
The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, USA.
Clin Genet. 1998 Mar;53(3):155-63. doi: 10.1111/j.1399-0004.1998.tb02666.x.
Holoprosencephaly (HPE), a common developmental defect affecting the forebrain and face, is etiologically heterogeneous and exhibits wide phenotypic variation. Graded degrees of severity of the brain malformation are also reflected in the highly variable craniofacial malformations associated with HPE. In addition, individuals with microforms of HPE, who usually have normal cognition and normal brain imaging, are at risk for having children with HPE. Some obligate carriers for HPE may not have any phenotypic abnormalities. Recurrent chromosomal rearrangements in individuals with HPE suggest loci containing genes important for brain development, and abnormalities in these genes may result in HPE. Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in humans. Proper function of SHH depends on cholesterol modification. Other candidate genes that may be involved in HPE include components of the SHH pathway, elements involved in cholesterol metabolism, and genes expressed in the developing forebrain.
前脑无裂畸形（HPE）是一种影响前脑和面部的常见发育缺陷，病因具有异质性，且表现出广泛的表型变异。脑畸形的严重程度分级也反映在与HPE相关的高度可变的颅面畸形中。此外，HPE微小型患者通常认知正常且脑成像正常，但他们生育患HPE孩子的风险较高。一些HPE的必然携带者可能没有任何表型异常。HPE患者的反复染色体重排提示了包含对脑发育重要基因的基因座，这些基因的异常可能导致HPE。最近，音猬因子（SHH）是首个被鉴定出可导致人类HPE的基因。SHH的正常功能依赖于胆固醇修饰。其他可能与HPE相关的候选基因包括SHH信号通路的组成部分、参与胆固醇代谢的元件以及在前脑发育过程中表达的基因。
