Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Clin Genet. 2013 Feb;83(2):169-74. doi: 10.1111/j.1399-0004.2012.01854.x. Epub 2012 Mar 16.
PLP1 (proteolipid protein1 gene) mutations cause Pelizaeus-Merzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array-based comparative genomic hybridization (a-CGH), we detected duplications at 22q13 and Xq22, encompassing 487-546 kb and 543-611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X-chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X-inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions.
PLP1（蛋白脂质蛋白 1 基因）突变导致佩利兹梅尔巴赫尔病（PMD），其特征是中枢神经系统脱髓鞘，几乎仅影响男性。我们报告了一例患有经典 PMD 的女孩，她携带明显平衡的易位 t(X;22)(q22;q13)。通过应用基于阵列的比较基因组杂交 (a-CGH)，我们在 22q13 和 Xq22 上检测到了分别包含 487-546 kb 和 543-611 kb 的重复序列。通过荧光原位杂交将额外的拷贝映射到衍生 X 染色体（22q13 重复片段）和衍生 22 号染色体（Xq22 重复片段）上的断点区域。在 14 个重复的 X 染色体基因中有一个是 PLP1。在大多数外周血白细胞中，正常的 X 染色体是无活性的，这种失活模式使细胞对易位片段在功能上达到平衡。然而，22 号染色体衍生染色体上的 PLP1 基因的一个拷贝，除了 X 和 der(X)染色体上的拷贝外，导致该基因的两个拷贝都是活跃的，而不管 X 失活模式如何，从而导致 PMD。这种 t(X;22)是第一个在断点区域检测到来自两个涉及染色体的重复的人类结构上平衡的易位。
