Atypical breakpoint in a t(6;17) translocation case of acampomelic campomelic dysplasia

Lauren C Walters-Sen; Devon Lamb Thrush; Scott E Hickey; Sayaka Hashimoto; Shalini Reshmi; Julie M Gastier-Foster; Robert E Pyatt; Caroline Astbury

doi:10.1016/j.ejmg.2014.04.018

Atypical breakpoint in a t(6;17) translocation case of acampomelic campomelic dysplasia

Eur J Med Genet. 2014 Jul;57(7):315-8. doi: 10.1016/j.ejmg.2014.04.018. Epub 2014 May 10.

Authors

Lauren C Walters-Sen¹, Devon Lamb Thrush², Scott E Hickey³, Sayaka Hashimoto¹, Shalini Reshmi⁴, Julie M Gastier-Foster⁵, Robert E Pyatt⁴, Caroline Astbury⁶

Affiliations

¹ Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.

PMID: 24821304
DOI: 10.1016/j.ejmg.2014.04.018

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.

Keywords: Campomelic dysplasia; FISH; SOX9; Sex reversal; Translocation.

Publication types

Case Reports

MeSH terms

Campomelic Dysplasia / genetics*
Chromosome Breakpoints
Chromosomes, Human, Pair 17 / genetics*
Chromosomes, Human, Pair 6 / genetics*
Female
Humans
Infant
SOX9 Transcription Factor / genetics*
Translocation, Genetic

Substances

SOX9 Transcription Factor
SOX9 protein, human