TY - JOUR
T1 - Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly
AU - Klopocki, Eva
AU - Kähler, Christian
AU - Foulds, Nicola
AU - Shah, Hitesh
AU - Joseph, Benjamin
AU - Vogel, Hermann
AU - Lüttgen, Sabine
AU - Bald, Rainer
AU - Besoke, Regina
AU - Held, Karsten
AU - Mundlos, Stefan
AU - Kurth, Ingo
N1 - Funding Information:
We thank the families for their cooperation and participation in this study. This study was supported by a grant to IK by the Fritz-Thyssen-Stiftung and to EK and SM by the Deutsche Forschungsgemeinschaft.
PY - 2012/6/1
Y1 - 2012/6/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ejhg.2011.264
DO - 10.1038/ejhg.2011.264
M3 - Article
C2 - 22258522
AN - SCOPUS:84861189609
SN - 1018-4813
VL - 20
SP - 705
EP - 708
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -