title: Atypical breakpoint in a t(6;17) translocation case of acampomelic campomelic dysplasia.
abstract: Campomelic dysplasia (CD) is a skeletal dysplasia characterized by Pierre Robin sequence (PRS), shortened and bowed long bones, airway instability, and the potential for sex reversal. A subtype of CD, acampomelic CD (ACD), is seen in approximately 10% of cases and preserves long bone straightness. Both syndromes are caused by alterations in SOX9, with translocations and missense mutations being overrepresented in ACD cases. We report a term infant with PRS, severe cervical spine abnormalities, eleven rib pairs, hypoplastic scapulae, and female genitalia. Chromosome analysis identified a 46,XY,t(6;17)(q25;q24) karyotype. FISH analysis with a series of BAC probes localized the translocation breakpoints to 6q27 and a region at 17q24.3 in the range of 459-379 kb upstream of SOX9. Therefore, this case extends the region classified as the proximal breakpoint cluster. In addition, the comorbidity of acampomelia, complete sex reversal, and severe spinal anomalies in our patient underscores the variability in the level of malformation in the CD/ACD family of disorders.
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Walters-Sen
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Devon Lamb
authors.initials: DL
authors.lastname: Thrush
authors.affiliation: Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA; Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hickey
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Reshmi
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Pyatt
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: Caroline.Astbury@nationwidechildrens.org.
authors.forename: Caroline
authors.initials: C
authors.lastname: Astbury
mesh_terms: D055036:Campomelic Dysplasia / Q000235:genetics*; D056905:Chromosome Breakpoints; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D055758:SOX9 Transcription Factor / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human
keywords: Campomelic dysplasia; FISH; SOX9; Sex reversal; Translocation