SOX9 基因重复与 46,XX 卵睾性发育障碍相关。

Duplication of SOX9 associated with 46,XX ovotesticular disorder of sex development.

机构信息

División de Investigación Biomédica, Subdirección de Enseñanza e Investigación, Centro Médico Nacional '20 de Noviembre', Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México DF, México.

Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México and Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF, México.

出版信息

Reprod Biomed Online. 2018 Jul;37(1):107-112. doi: 10.1016/j.rbmo.2018.03.017. Epub 2018 Apr 4.

DOI:10.1016/j.rbmo.2018.03.017

PMID:29673731

Abstract

RESEARCH QUESTION

The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease.

DESIGN

Ten unrelated SRY-negative 46,XX ovotesticular disorder of sexual development (DSD) subjects were molecularly studied. Multiplex-ligation dependent probe amplification (MLPA) and quantitative real-time PCR analysis (qRT-PCR) for SOX9 were performed.

RESULTS

The MLPA analysis demonstrated that one patient presented a heterozygous duplication of the entire SOX9 coding region (above 1.3 value of peak ratio), as well as at least a ~ 483 kb upstream duplication. Moreover, no duplication of other SOX9 probes was observed corresponding to the region between -1007 and -1500 kb upstream. A qRT-PCR analysis showed a duplication of at least -581 kb upstream and ~1.63 kb of the coding region that encompasses exon 3. The limits of the duplication were mapped approximately from ~71539762 to 72122741 of Chr17. No molecular abnormalities were found in the remaining nine patients.

CONCLUSION

This study is thought to be the first report regarding a duplication of SOX9 that is associated with the presence of 46,XX ovotesticular DSD, encompassing at least -581 kb upstream, and the almost entire coding region of the gene.

摘要

研究问题

本研究旨在探讨 10 名与 SRY 无关的具有这种性别分化障碍的 46,XX 卵睾性发育障碍 (DSD) 个体是否存在双倍剂量的 SOX9，作为其疾病的原因。

设计

对 10 名与 SRY 无关的 46,XX 卵睾性发育障碍 (DSD) 个体进行了分子研究。进行了多重连接依赖性探针扩增 (MLPA) 和 SOX9 的定量实时 PCR 分析 (qRT-PCR)。

结果

MLPA 分析表明，一名患者存在整个 SOX9 编码区的杂合性重复（峰比超过 1.3），以及至少一个 ~483kb 的上游重复。此外，在 -1007 至 -1500kb 上游区域之间没有观察到其他 SOX9 探针的重复。qRT-PCR 分析显示，至少在 -581kb 上游和包含外显子 3 的 ~1.63kb 的编码区存在重复。重复的界限大致从 Chr17 的 ~71539762 到 72122741 映射。在其余 9 名患者中未发现分子异常。