Oneda Beatrice, Asadollahi Reza, Azzarello-Burri Silvia, Niedrist Dunja, Baldinger Rosa, Masood Rahim, Schinzel Albert, Latal Bea, Jenni Oskar G, Rauch Anita
Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland.
Mol Syndromol. 2017 Aug;8(5):266-271. doi: 10.1159/000477189. Epub 2017 Jun 13.
Chromosomal mosaicism, which represents a diagnostic challenge for detection and interpretation, has been described in several genetic conditions. It can contribute to a large phenotypic variation in diseases. At analysis of a well-characterized cohort of 714 patients with neurodevelopmental disorders (NDDs) of unknown etiology using a high-resolution chromosomal microarray platform, we found 2 cases (0.28%) of low-level mosaicism and defined a previously detected extra chromosome in a third patient. Two of the cases were mosaics for segmental imbalances (a partial trisomy 3q26.1q27.3 and a partial monosomy 18q21.2qter with 14.6 and 20% mosaic ratios in lymphocytes, respectively), and 1 was a mosaic for an entire chromosome (trisomy 14, mosaic ratio 20%). Our diagnostic yield is in line with the ratios previously published in patients with intellectual disability. Notably, the partial trisomy 3q26.1q27.3 case is an example of a rare and unusual class of a rearranged neocentric ring chromosome, which can neither be categorized in class I, nor in class II of such rearrangements. Our cases further elucidate the phenotypes related to the aberrations of the specific chromosome segments observed and underline the important role of low-level mosaics in the pathogenesis of NDDs of unknown etiology even in the absence of clinical signs of mosaicism.
染色体嵌合体在多种遗传疾病中均有描述，这给检测和解读带来了诊断挑战。它可导致疾病中出现较大的表型变异。在使用高分辨率染色体微阵列平台对714例病因不明的神经发育障碍（NDD）患者进行特征明确的队列分析时，我们发现了2例（0.28%）低水平嵌合体病例，并确定了第三例患者之前检测到的一条额外染色体。其中2例为节段性失衡嵌合体（分别为部分3号染色体q26.1q27.3三体和部分18号染色体q21.2qter单体，淋巴细胞中的嵌合比例分别为14.6%和20%），1例为整条染色体嵌合体（14号染色体三体，嵌合比例20%）。我们的诊断率与先前发表的智力残疾患者的比例一致。值得注意的是，部分3号染色体q26.1q27.3三体病例是一种罕见且特殊的重排新着丝粒环形染色体的例子，这种染色体既不能归类于此类重排的I类，也不能归类于II类。我们的病例进一步阐明了与观察到的特定染色体片段畸变相关的表型，并强调了低水平嵌合体在病因不明的NDD发病机制中的重要作用，即使在没有嵌合体临床体征的情况下也是如此。
