BackgroundMutations in known causative genes and cytogenetically detectable chromosomal rearrangements account for a fraction of cases with 46,XY disorders of sex development (DSD). Recent advances in molecular cytogenetic technologies, including array-based comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA), have enabled the identification of copy-number variations (CNVs) in individuals with apparently normal karyotypes.FindingsThis review paper summarizes the results of 15 recent studies, in which aCGH or MLPA were used to identify CNVs. Several submicroscopic CNVs have been detected in patients with 46,XY DSD. These CNVs included deletions involving known causative genes such as DMRT1 or NR5A1, duplications involving NR0B1, deletions involving putative cis-regulatory elements of SOX9, and various deletions and duplications of unknown pathogenicity.ConclusionsThe results of recent studies highlight the significance of submicroscopic CNVs as the genetic basis of 46,XY DSD. Molecular cytogenetic analyses should be included in the diagnostic workup of patients with 46,XY DSD of unknown origin. Further studies using aCGH will serve to clarify novel causes of this condition.

中文翻译：

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与 46,XY 性发育障碍相关的亚显微拷贝数变异

背景已知致病基因的突变和细胞遗传学可检测的染色体重排占 46,XY 性发育障碍 (DSD) 病例的一小部分。分子细胞遗传学技术的最新进展，包括基于阵列的比较基因组杂交 (aCGH) 和多重连接依赖性探针扩增 (MLPA)，已经能够识别具有明显正常核型的个体的拷贝数变异 (CNV)。总结了最近 15 项研究的结果，其中使用 aCGH 或 MLPA 来识别 CNV。已在 46,XY DSD 患者中检测到几种亚显微 CNV。这些 CNV 包括涉及已知致病基因（如 DMRT1 或 NR5A1）的缺失、涉及 NR0B1 的重复、涉及 SOX9 的假定顺式调控元件的缺失、以及未知致病性的各种缺失和重复。结论最近的研究结果强调了亚显微 CNV 作为 46,XY DSD 遗传基础的重要性。分子细胞遗传学分析应包括在不明来源的 46,XY DSD 患者的诊断检查中。使用 aCGH 的进一步研究将有助于阐明这种情况的新原因。