Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in-house-designed synthetic probe set for multiplex ligation-dependent probe amplification analysis
Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in-house-designed synthetic probe set for multiplex ligation-dependent probe amplification analysis
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DOI：
10.1111/j.1399-0004.2008.00980.x
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Oscarson, M.
中科院分区：
文献类型：
--
作者：
Barbaro, M.;Cicognani, A.;Oscarson, M.
睾丸的发育需要SRY基因和其他以剂量敏感方式起作用的基因的适当时空表达。SRY基因突变仅占46，XY性腺性发育障碍（DSD）患者的10-15%。为了能够诊断已知参与不同形式的DSD的基因的缺失和重复，我们开发了用于多重连接依赖性探针扩增（MLPA）分析的合成探针组。本文报告22例46，XY性腺发育不全患者的分析结果。与DSD探针集的分析导致了两个拷贝数的变化，800 kb的NR 0 B1（DAX 1）基因座重复Xp 21在患者与孤立的部分性腺发育不全和重复的SRD 5A 2基因，代表一种罕见的正常变异的鉴定。所描述的MLPA试剂盒代表了DSD患者DNA序列分析的最佳补充，能够同时筛查几个基因的缺失和重复。此外，第二次鉴定的NR 0 B1基因座重复的患者孤立的性腺发育不全，没有畸形的功能和/或精神发育迟滞，突出了评估NR 0 B1重复的重要性，性腺发育不全的患者。
The development of a testis requires the proper spatiotemporal expression of the SRY gene and other genes that act in a dosage-sensitive manner. Mutations in the SRY gene account for only 10-15% of patients with 46,XY gonadal disorder of sex development (DSD). To enable the diagnostics of deletions and duplications of genes known to be involved in different forms of DSD, we developed a synthetic probe set for multiplex ligation-dependent probe amplification (MLPA) analysis. Here, we report the results from the analysis of 22 patients with 46,XY gonadal DSD. The analysis with the DSD probe set has led to the identification of two copy number variations, an 800-kb NR0B1 (DAX1) locus duplication on Xp21 in a patient with isolated partial gonadal dysgenesis and a duplication of the SRD5A2 gene that represents a rare normal variant. The described MLPA kit represents an optimal complement to DNA sequence analysis in patients with DSD, enabling screening for deletions and duplications of several genes simultaneously. Furthermore, the second identification of an NR0B1 locus duplication in a patient with isolated gonadal dysgenesis, without dysmorphic features and/or mental retardation, highlights the importance of evaluating NR0B1 duplication in patients with gonadal dysgenesis.