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

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

来源：European Journal of Medical Genetics, 2014, 57(7): 315-318.

DOI：10.1016/j.ejmg.2014.04.018

• SOX9
• Campomelic dysplasia
• Translocation
• Sex reversal
• FISH

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 over-represented 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.

• 出版日期2014-7