Li Xiaoyan, Xie Hua, Chen Qian, Yu Xiongying, Yi Zhaoshi, Li Erzhen, Zhang Ting, Wang Jian, Zhong Jianmin, Chen Xiaoli
Department of Neurology, Jiangxi Children's Hospital, Yangming Road, Donghu District, Nanchang, 330006, China.
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Room 616, NO. 2, Yabao Road, Chaoyang District, Beijing, 100020, China.
BMC Med Genet. 2017 Nov 15;18(1):131. doi: 10.1186/s12881-017-0486-4.
Chromosomal duplication at the Xq28 region including the MECP2 gene, share consistent clinical phenotypes and a distinct facial phenotype known as MECP2 duplication syndrome. The typical clinical features include infantile hypotonia , mild dysmorphic features, a broad range of neurodevelopmental disorders, recurrent infections, and progressive spasticity.
This Chinese MECP2 duplication syndrome family includes six patients (five males and one female), and four asymptomatic female carriers. Two kinds of chips including 4x180K CNV + SNP chip and custom 8x60K CNV chip were used to detect MECP2 duplication, and then fluorescent in situ hybridization (FISH) analysis was performed to identify the exact copy number of MECP2. X-chromosome inactivation (XCI) analysis on AR gene was detected for all female family members, and the m icrosatellite analysis on MECP2 was used to validate the recombination event on MECP2 region.
The affected male subjects presented with a broad range of neurodevelopmental symptoms (severe intellectual disability, developmental delay, seizure, language deficit, and autism spectrum disorder) as well as facial dysmorphism and other symptoms which were consistent with that of Western patients previous reported. Seizure is reported in Chinese patients for the first time. In addition, we validated three recombination events for the MECP2-duplication allele during maternal transmission due to X homologous recombination.
We provided the largest known Chinese pedigree with MECP2 duplication syndrome. The detailed clinical description and molecular genetic characterization in all affected family members further delineate the typical phenotype of this genomic disorder in Chinese population.
Xq28区域的染色体重复，包括MECP2基因，具有一致的临床表型和一种独特的面部表型，称为MECP2重复综合征。典型的临床特征包括婴儿期肌张力减退、轻度畸形特征、广泛的神经发育障碍、反复感染和进行性痉挛。
这个中国MECP2重复综合征家系包括6名患者（5名男性和1名女性）以及4名无症状女性携带者。使用两种芯片，即4x180K CNV + SNP芯片和定制的8x60K CNV芯片来检测MECP2重复，然后进行荧光原位杂交（FISH）分析以确定MECP2的确切拷贝数。对所有女性家庭成员进行AR基因的X染色体失活（XCI）分析，并使用MECP2的微卫星分析来验证MECP2区域的重组事件。
受影响的男性受试者表现出广泛的神经发育症状（严重智力残疾、发育迟缓、癫痫、语言缺陷和自闭症谱系障碍）以及面部畸形和其他症状，这与先前报道的西方患者一致。癫痫在中国患者中首次被报道。此外，我们验证了由于X同源重组在母系传递过程中MECP2重复等位基因的三个重组事件。
我们提供了已知最大的中国MECP2重复综合征家系。所有受影响家庭成员的详细临床描述和分子遗传学特征进一步描绘了中国人群中这种基因组疾病的典型表型。
