title: Duplication of PTHLH causes osteochondroplasia with a combined brachydactyly type E/A1 phenotype with disturbed bone maturation and rhizomelia.
abstract: Parathyroid hormone-like hormone (PTHLH, MIM 168470) plays an important role in endochondral bone development and prevents chondrocytes from differentiating. Disease-causing variants and haploinsufficiency of PTHLH are known to cause brachydactyly type E and short stature. So far, three large duplications encompassing several genes including PTHLH associating with enchondromatas and acro-osteolysis have been described in the literature. Here, we report on a three-generation pedigree with short humerus, curved radius, and a specific type of severe brachydactyly with features of types E and A1 but without the enchondromatas and the acro-osteolysis. Microarray-based comparative genomic hybridization (array-CGH) revealed a 70-kb duplication on chromosome 12p11.22 encompassing only PTHLH. Our data extend the phenotypic spectrum associated with copy number variations of PTHLH, and this family is to our knowledge the first description harboring a microduplication encompassing only PTHLH.
authors.affiliation: Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Flöttmann
authors.affiliation: Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sowinska-Seidler
authors.affiliation: Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), Université de Bordeaux, EA4576, Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lavie
authors.affiliation: Department of Pediatric Radiology, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Chateil
authors.affiliation: Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), Université de Bordeaux, EA4576, Bordeaux, France.|Department of Medical Genetics, CHU de Bordeaux, Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.|Max Planck Institute for Molecular Genetics, Berlin, Germany.|Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.affiliation: Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.affiliation: Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.|Max Planck Institute for Molecular Genetics, Berlin, Germany.|Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Spielmann
mesh_terms: D000328:Adult; D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000235:genetics*; D059327:Brachydactyly / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D005269:Femur / Q000002:abnormalities*; D020440:Gene Duplication; D006801:Humans; D006811:Humerus / Q000002:abnormalities*; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein