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Free keywords:
Bone Diseases, Developmental/genetics/metabolism
Clubfoot/genetics/pathology
Ectromelia/genetics/metabolism
Gene Expression Regulation, Developmental
Heterozygote
Humans
Lower Extremity/embryology/ pathology
Paired Box Transcription Factors/ genetics
Polydactyly/ genetics/pathology
Sequence Deletion
Tibia/abnormalities/metabolism
Abstract:
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.
