Autor(es)

Fonseca, Ana Carolina S. ^[1] ; Bonaldi, Adriano ^[1] ; Bertola, Debora R. ^{[1, 2]} ; Kim, Chong A. ^[2] ; Otto, Paulo A. ^[1] ; Vianna-Morgante, Angela M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo - Brazil

^[2] HC FMUSP, Inst Crianca, Unidade Genet, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC MEDICAL GENETICS; v. 14, MAY 7 2013.
• Citações Web of Science: 20

Resumo

Background: The association of balanced rearrangements with breakpoints near SOX9 {[}SRY (sex determining region Y)-box 9] with skeletal abnormalities has been ascribed to the presumptive altering of SOX9 expression by the direct disruption of regulatory elements, their separation from SOX9 or the effect of juxtaposed sequences. Case presentation: We report on two sporadic apparently balanced translocations, t(7;17)(p13;q24) and t(17; 20) (q24.3;q11.2), whose carriers have skeletal abnormalities that led to the diagnosis of acampomelic campomelic dysplasia (ACD; MIM 114290). No pathogenic chromosomal imbalances were detected by a-CGH. The chromosome 17 breakpoints were mapped, respectively, 917-855 kb and 601-585 kb upstream of the SOX9 gene. A distal cluster of balanced rearrangements breakpoints on chromosome 17 associated with SOX9-related skeletal disorders has been mapped to a segment 932-789 kb upstream of SOX9. In this cluster, the breakpoint of the herein described t(17;20) is the most telomeric to SOX9, thus allowing the redefining of the telomeric boundary of the distal breakpoint cluster region related to skeletal disorders to 601-585 kb upstream of SOX9. Although both patients have skeletal abnormalities, the t(7;17) carrier presents with relatively mild clinical features, whereas the t(17;20) was detected in a boy with severe broncheomalacia, depending on mechanical ventilation. Balanced and unbalanced rearrangements associated with disorders of sex determination led to the mapping of a regulatory region of SOX9 function on testicular differentiation to a 517-595 kb interval upstream of SOX9, in addition to TESCO (Testis-specific enhancer of SOX9 core). As the carrier of t(17;20) has an XY sex-chromosome constitution and normal male development for his age, the segment of chromosome 17 distal to the translocation breakpoint should contain the regulatory elements for normal testis development. Conclusions: These two novel translocations illustrate the clinical variability in carriers of balanced translocations with breakpoints near SOX9. The translocation t(17;20) breakpoint provides further evidence for an additional testis-specific SOX9 enhancer 517 to 595 kb upstream of the SOX9 gene. (AU)

• Processo FAPESP: 09/03480-8 - Caracterização de rearranjos cromossômicos aparentemente equilibrados associados a quadros clínicos: mapeamento dos pontos de quebra e triagem de deleções e duplicações submicroscópicas
• Beneficiário: Ana Carolina dos Santos Fonseca
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/12486-0 - Análise da expressão de genes sujeitos a imprinting genômico e de microrrearranjos cromossômicos em pacientes com distúrbios de crescimento associados ou não a deficiência mental
• Beneficiário: Adriano Bonaldi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/14293-4 - Caracterização de rearranjos cromossômicos aparentemente equilibrados e sua relação com o fenótipo dos portadores
• Beneficiário: Ana Carolina dos Santos Fonseca
• Modalidade de apoio: Bolsas no Brasil - Doutorado