Abstract：
To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases.
In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50-100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12.
The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.
In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50-100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12.
The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.
摘要：
迄今为止,仅报告了21例出生后诊断为马赛克三体性12的病例。最常见的表型表现是发育迟缓，畸形面部特征，先天性心脏缺陷,数字改动,和色素性疾病。在本报告中，本文描述了3例无亲缘关系的新出现的镶嵌三体性12患者的详细临床和基因概况,并与以前报道的病例进行了比较.
在本报告中，我们包括临床，细胞遗传学，和三名墨西哥患者的分子描述出生后诊断为镶嵌三体12。在表型水平，三名患者出现发育迟缓，畸形面部特征，先天性心脏缺陷和皮肤色素异常。特别是,患者1表现出独特的眼部改变为双侧扩张症，三排上睫毛，和数字异常。在患者2多余的皮肤中，严重的听力损失,并观察到低张力，3例患者表现为过度远调和远视。具有播散性色素异常的色素沉着过度是所有这些中的共同特征。细胞遗传学研究是在严格的分析标准下进行的,从三个不同的组织中筛选50-100个中期，在所分析的三种不同组织中的至少一种中显示出12三体镶嵌性。有了SNParray,先前未被细胞遗传学检测到的低水平马赛克拷贝数变异的存在，排除了12号染色体的单亲染色体。STR标记允许确认不存在单亲二倍体，并知道多余染色体12的亲本起源。
详细的临床，细胞遗传学，以及这三个新患者的分子描述，有助于相关信息更准确地描绘一组表现出异质性表型的患者，虽然共享相同的染色体改变。检测镶嵌三体性12的可能性与用于揭示低水平染色体镶嵌性的方法的灵敏度直接相关。以及在合适的组织中进行分析的可能性。
在本报告中，我们包括临床，细胞遗传学，和三名墨西哥患者的分子描述出生后诊断为镶嵌三体12。在表型水平，三名患者出现发育迟缓，畸形面部特征，先天性心脏缺陷和皮肤色素异常。特别是,患者1表现出独特的眼部改变为双侧扩张症，三排上睫毛，和数字异常。在患者2多余的皮肤中，严重的听力损失,并观察到低张力，3例患者表现为过度远调和远视。具有播散性色素异常的色素沉着过度是所有这些中的共同特征。细胞遗传学研究是在严格的分析标准下进行的,从三个不同的组织中筛选50-100个中期，在所分析的三种不同组织中的至少一种中显示出12三体镶嵌性。有了SNParray,先前未被细胞遗传学检测到的低水平马赛克拷贝数变异的存在，排除了12号染色体的单亲染色体。STR标记允许确认不存在单亲二倍体，并知道多余染色体12的亲本起源。
详细的临床，细胞遗传学，以及这三个新患者的分子描述，有助于相关信息更准确地描绘一组表现出异质性表型的患者，虽然共享相同的染色体改变。检测镶嵌三体性12的可能性与用于揭示低水平染色体镶嵌性的方法的灵敏度直接相关。以及在合适的组织中进行分析的可能性。
