title: A new acro-osteolysis syndrome caused by duplications including PTHLH.
abstract: Parathyroid hormone-like hormone (PTHLH, MIM 168470) is a humoral factor, structurally and functionally related to parathyroid hormone, which mediates multiple effects on chondrocyte, osteoblast and osteoclast function. Mutations and copy number imbalances of the PTHLH locus and in the gene encoding its receptor, PTHR1, result in a variety of skeletal dysplasias including brachydactyly type E, Eiken syndrome, Jansen metaphyseal chondrodysplasia and Blomstrand type chondrodysplasia. Here we describe three individuals with duplications of the PTHLH locus, including two who are mosaic for these imbalances, leading to a hitherto unrecognized syndrome characterized by acro-osteolysis, cortical irregularity of long bones and metadiaphyseal enchondromata.
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Gray
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Margriet
authors.initials: M
authors.lastname: van Kogelenberg
authors.affiliation: Cytogenetics Laboratory, Genetics Health Service New Zealand, Wellington Hospital, Wellington, New Zealand.
authors.forename: Rachel
authors.initials: R
authors.lastname: Beddow
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Tim
authors.initials: T
authors.lastname: Morgan
authors.affiliation: Nuffield Orthopaedic Centre, Department of Rheumatology, Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Wordsworth
authors.affiliation: Oxford Regional Genetics Service, The Churchill Hospital, Oxford, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Shears
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.affiliation: Department of Genetics, The Hospital for Sick Children, London, UK.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hurst
mesh_terms: D030981:Acro-Osteolysis / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005192:Family Health; D005260:Female; D020440:Gene Duplication; D031845:Hajdu-Cheney Syndrome / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein