title: Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly.
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.
authors.affiliation: Institut für Medizinische Genetik und Humangenetik, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Christian
authors.initials: C
authors.lastname: Kähler
authors.forename: Nicola
authors.initials: N
authors.lastname: Foulds
authors.forename: Hitesh
authors.initials: H
authors.lastname: Shah
authors.forename: Benjamin
authors.initials: B
authors.lastname: Joseph
authors.forename: Hermann
authors.initials: H
authors.lastname: Vogel
authors.forename: Sabine
authors.initials: S
authors.lastname: Lüttgen
authors.forename: Rainer
authors.initials: R
authors.lastname: Bald
authors.forename: Regina
authors.initials: R
authors.lastname: Besoke
authors.forename: Karsten
authors.initials: K
authors.lastname: Held
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: Ingo
authors.initials: I
authors.lastname: Kurth
mesh_terms: D001848:Bone Diseases, Developmental / Q000235:genetics / Q000378:metabolism; D003025:Clubfoot / Q000235:genetics / Q000473:pathology; D004480:Ectromelia / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006801:Humans; D035002:Lower Extremity / Q000196:embryology / Q000473:pathology*; D051761:Paired Box Transcription Factors / Q000235:genetics*; D017689:Polydactyly / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D013977:Tibia / Q000002:abnormalities / Q000378:metabolism
chemical_list: D051761:Paired Box Transcription Factors; C101485:homeobox protein PITX1