Institut für Medizinische Genetik und Humangenetik, Charité Universitätsmedizin Berlin, Berlin, Germany.
Eur J Hum Genet. 2012 Jun;20(6):705-8. doi: 10.1038/ejhg.2011.264. Epub 2012 Jan 18.
PITX1 is a bicoid-related homeodomain transcription factor implicated in vertebrate hindlimb development. Recently, mutations in PITX1 have been associated with autosomal-dominant clubfoot. In addition, one affected individual showed a polydactyly and right-sided tibial hemimelia. We now report on PITX1 deletions in two fetuses with a high-degree polydactyly, that is, mirror-image polydactyly. Analysis of DNA from additional individuals with isolated lower-limb malformations and higher-degree polydactyly identified a third individual with long-bone deficiency and preaxial polydactyly harboring a heterozygous 35 bp deletion in PITX1. The findings demonstrate that mutations in PITX1 can cause a broad spectrum of isolated lower-limb malformations including clubfoot, deficiency of long bones, and mirror-image polydactyly.
PITX1 是一种与 bicoid 相关的同源域转录因子，参与脊椎动物后肢发育。最近，PITX1 的突变与常染色体显性的马蹄内翻足有关。此外，一个受影响的个体还表现出多指畸形和右侧胫骨半肢畸形。我们现在报告了两个具有高度多指畸形（即镜像多指畸形）的胎儿的 PITX1 缺失。对具有孤立下肢畸形和高度多指畸形的其他个体的 DNA 进行分析，发现了第三个个体存在长骨缺乏和桡侧多指畸形，携带有 PITX1 中的杂合 35 个碱基对缺失。这些发现表明，PITX1 突变可导致广泛的孤立下肢畸形，包括马蹄内翻足、长骨缺失和镜像多指畸形。
