title: Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly.
abstract: Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient.
authors: Department of Clinical Genetics, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors: Elisabeth M
authors: EM
authors: Lodder
authors: Bert H
authors: BH
authors: Eussen
authors: Daniëlla A C M
authors: DA
authors: van Hassel
authors: A Jeannette M
authors: AJ
authors: Hoogeboom
authors: Pino J
authors: PJ
authors: Poddighe
authors: J Henk
authors: JH
authors: Coert
authors: Ben A
authors: BA
authors: Oostra
authors: Annelies
authors: A
authors: de Klein
authors: Esther
authors: E
authors: de Graaff
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D005532:Foot Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006228:Hand Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D017689:Polydactyly / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; C088144:HoxA protein