title: Familial acampomelic form of campomelic dysplasia caused by a 960 kb deletion upstream of SOX9.
abstract: Campomelic dysplasia (CD) is a rare autosomal dominant osteochondrodysplasia with or without XY disorders of sexual development (DSD). Campomelia is absent in about 10% of the cases, referred to as the acampomelic form of CD (ACD). Most CDs are caused by mutations within the SOX9 coding region. Several CD patients with balanced chromosome rearrangements involving the 17q24 region have been reported suggesting the presence of cis-regulatory elements upstream and/or downstream of the gene. Deletions upstream of SOX9 represent a third mechanism of mutation. To date, a 1.5 Mb de novo deletion in the SOX9 upstream region has been identified in a single 46,XY patient with ACD and DSD. We report here for the first time on a familial ACD caused by an inherited deletion mapping upstream of the SOX9 gene. Using high-density oligoarray comparative genomic hybridization (CGH), we showed that the size of the deletion was 960 kb in the XY-DSD child and her mother, both affected. The deletion lying from 517 kb to 1.477 Mb upstream of SOX9 remove several highly conserved elements and reduce the minimum critical size and therefore the number of highly conserved sequence elements responsible for ACD.
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lecointre
authors.forename: Olivier
authors.initials: O
authors.lastname: Pichon
authors.forename: Antoine
authors.initials: A
authors.lastname: Hamel
authors.forename: Yves
authors.initials: Y
authors.lastname: Heloury
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel-Calemard
authors.forename: Yves
authors.initials: Y
authors.lastname: Morel
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
mesh_terms: D001483:Base Sequence; D055036:Campomelic Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008969:Molecular Sequence Data; D009035:Mothers; D009679:Nuclear Family; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020161:Physical Chromosome Mapping; D011859:Radiography; D055758:SOX9 Transcription Factor / Q000235:genetics*; D017384:Sequence Deletion; D014463:Ultrasonography
chemical_list: D055758:SOX9 Transcription Factor; D004247:DNA