Medical Genetics, Department of Medicine, Surgery and Dentistry, Università degli Studi di Milano, Italy.
Genet Med. 2010 Oct;12(10):634-40. doi: 10.1097/GIM.0b013e3181ed6185.
The Mayer-Rokitansky-Küster-Hauser syndrome is defined as congenital aplasia of müllerian ducts derived structures in females with a normal female chromosomal and gonadal sex. Most cases with Mayer-Rokitansky-Küster-Hauser syndrome are sporadic, although familial cases have been reported. The genetic basis of Mayer-Rokitansky-Küster-Hauser syndrome is largely unknown and seems heterogeneous, and a small number of cases were found to have mutations in the WNT4 gene. The aim of this study was to identify possible recurrent submicroscopic imbalances in a cohort of familial and sporadic cases with Mayer-Rokitansky-Küster-Hauser syndrome.
Multiplex ligation-dependent probe amplification was used to screen the subtelomeric sequences of all chromosomes in 30 patients with Mayer-Rokitansky-Küster-Hauser syndrome (sporadic, n = 27 and familial, n = 3). Segregation analysis and pyrosequencing were applied to validate the MLPA results in the informative family.
Partial duplication of the Xpter pseudoautosomal region 1 containing the short stature homeobox (SHOX) gene was detected in five patients with Mayer-Rokitansky-Küster-Hauser syndrome (familial, n = 3 and sporadic, n = 2) and not in 53 healthy controls. The duplications were not overlapping, and SHOX was never entirely duplicated. Haplotyping in the informative family revealed that SHOX gene duplication was inherited from the unaffected father and was absent in two healthy sisters.
Partial duplication of SHOX gene is found in some cases with both familial and sporadic Mayer-Rokitansky-Küster-Hauser type I syndrome.
Mayer-Rokitansky-Küster-Hauser 综合征被定义为女性中 Müllerian 管衍生结构的先天性发育不全，具有正常的女性染色体和性腺性别。大多数 Mayer-Rokitansky-Küster-Hauser 综合征病例是散发性的，尽管也有家族性病例报道。Mayer-Rokitansky-Küster-Hauser 综合征的遗传基础在很大程度上尚不清楚，似乎具有异质性，少数病例发现 WNT4 基因存在突变。本研究旨在鉴定 Mayer-Rokitansky-Küster-Hauser 综合征的家族性和散发性病例队列中可能存在的反复亚微观不平衡。
使用多重连接依赖性探针扩增法对 30 名 Mayer-Rokitansky-Küster-Hauser 综合征患者（散发性，n=27 例和家族性，n=3 例）的所有染色体端粒序列进行筛选。应用分离分析和焦磷酸测序对信息丰富的家系中的 MLPA 结果进行验证。
在 5 名 Mayer-Rokitansky-Küster-Hauser 综合征患者（家族性，n=3 例和散发性，n=2 例）中检测到包含矮小同源盒（SHOX）基因的 Xpter 假常染色体区域 1 的部分重复，而在 53 名健康对照中未检测到。重复并不重叠，且 SHOX 从未完全重复。信息丰富的家系中的单体型分析表明，SHOX 基因重复是从未受影响的父亲遗传而来，且在两名健康的姐妹中均不存在。
部分 SHOX 基因重复可见于一些家族性和散发性 Mayer-Rokitansky-Küster-Hauser Ⅰ型综合征病例中。
