Xu Fang, Zhang Ya-Nan, Cheng De-Hua, Tan Ke, Zhong Chang-Gao, Lu Guang-Xiu, Lin Ge, Tan Yue-Qiu
Institute of Reproduction and Stem Cell Engineering, Central South University, 110# Xiangya Road, Changsha, Hunan 410078 PR China ; Reproductive and Genetic Hospital of Citic-Xiangya, Changsha, Hunan 410078 PR China.
Institute of Reproduction and Stem Cell Engineering, Central South University, 110# Xiangya Road, Changsha, Hunan 410078 PR China.
Mol Cytogenet. 2014 Oct 3;7(1):64. doi: 10.1186/s13039-014-0064-9. eCollection 2014.
Copy Number Variants (CNVs) is a new molecular frontier in clinical genetics. CNVs in 1p36 are usually pathogenic and have attracted the attention of cytogeneticists worldwide. None of 1p36 triplication has been reported thus far.
We present three patients with CNVs in 1p36. Among them one is the first 1p36 tetrasomy due to a pure microtriplication and the other two are 1p36 microdeletion. Traditional chromosome G-banding technique showed a normal karyotype. Single nucleotide polymorphism (SNP) microarray analysis combined with multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to identify and confirm the chromosome microdeletion/microtriplication. The facial dysmorphisms of the patient with 1p36 tetrasomy differed from those two patients with 1p36 monosomy. The expression levels of B3GALT6, MIB2, PEX10 and PANK4 in the blood were determined, and differential expressions were observed between the patients and controls.
Our study shows the first case of 1p36 tetrasomy due to a pure microtriplication in a patient with severe intellectual disability and seizures. The study provides a new resource for studying the mechanisms of microtriplication formation, and provides an evidence that overexpression of the specific genes might be related the specific phenotype of 1p36 microtriplication.
拷贝数变异（CNVs）是临床遗传学中的一个新的分子前沿领域。1p36区域的CNVs通常具有致病性，已引起全球细胞遗传学家的关注。迄今为止，尚未有1p36三倍体的报道。
我们报告了3例1p36区域存在CNVs的患者。其中1例是由于单纯的微三倍体导致的首例1p36四体，另外2例是1p36微缺失。传统的染色体G显带技术显示核型正常。采用单核苷酸多态性（SNP）微阵列分析联合多重连接依赖探针扩增（MLPA）和荧光原位杂交（FISH）技术来鉴定和确认染色体微缺失/微三倍体。1p36四体患者的面部畸形与另外2例1p36单体患者不同。测定了血液中B3GALT6、MIB2、PEX10和PANK4的表达水平，观察到患者与对照组之间存在差异表达。
我们的研究显示了首例因单纯微三倍体导致1p36四体的严重智力障碍和癫痫患者。该研究为研究微三倍体形成机制提供了新的资源，并提供了证据表明特定基因的过表达可能与1p36微三倍体的特定表型有关。
