A Complex 6p25 Rearrangement in a Child With Multiple Epiphyseal Dysplasia

作者：Bedoyan Jirair K^*; Lesperance Marci M; Ackley Todd; Iyer Ramaswamy K; Innis Jeffrey W; Misra Vinod K

来源：American Journal of Medical Genetics, Part A, 2011, 155A(1): 154-163.

DOI：10.1002/ajmg.a.33751

• 6p25
• FOXC1
• epiphyseal dysplasia
• rearrangement
• aCGH
• SNP array
• TaqMan (R)

Genomic rearrangements are increasingly recognized as important contributors to human disease. Here we report on an 11 1/2-year-old child with myopia, Duane retraction syndrome, bilateral mixed hearing loss, skeletal anomalies including multiple epiphyseal dysplasia, and global developmental delay, and a complex 6p25 genomic rearrangement. We have employed oligonucleotide-based comparative genomic hybridization arrays (aCGH) of different resolutions (44 and 244K) as well as a 1Msingle nucleotide polymorphism (SNP) array to analyze this complex rearrangement. Our analyses reveal a complex rearrangement involving a similar to 2.21Mb interstitial deletion, a similar to 240 kb terminal deletion, and a 70-80 kb region in between these two deletions that shows maintenance of genomic copy number. The interstitial deletion contains eight known genes, including three Forkhead box containing (FOX) transcription factors (FOXQ1, FOXF2, and FOXC1). The region maintaining genomic copy number partly overlaps the dual specificity protein phosphatase 22 (DUSP22) gene. Array analyses suggest a homozygous loss of genomic material at the 50 end of DUSP22, which was corroborated using TaqMan (R) copy number analysis. It is possible that this homozygous genomic loss may render both copies of DUSP22 or its products non-functional. Our analysis suggests a rearrangement mechanism distinct from a previously reported replication-based error-prone mechanism without template switching for a specific 6p25 rearrangement with a 1.22Mb interstitial deletion. Our study demonstrates the utility and limitations of using oligonucleotide-based aCGH and SNP array technologies of increasing resolutions in order to identify complex DNA rearrangements and gene disruptions.

• 出版日期2011-1