PDF(Pubmed)
Abstract：
BACKGROUND: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males. It is characterized by delayed or absent speech development, severe motor and cognitive impairment, and recurrent respiratory infections. MDS is caused by the duplication of a chromosomal region located on chromosome Xq28, which contains the methyl CpG binding protein-2 (MECP2) gene. MECP2 functions as a transcriptional repressor or activator, regulating genes associated with nervous system development. The objective of this study is to provide a clinical description of MDS, including imaging changes observed from the fetal period to the neonatal period.
METHODS: Conventional G-banding was employed to analyze the chromosome karyotypes of all pedigrees under investigation. Subsequently, whole exome sequencing (WES), advanced biological information analysis, and pedigree validation were conducted, which were further confirmed by copy number variation sequencing (CNV-seq).
RESULTS: Chromosome karyotype analysis revealed that a male patient had a chromosome karyotype of 46,Y,dup(X)(q27.2q28). Whole-exon duplication in the MECP2 gene was revealed through WES results. CNV-seq validation confirmed the presence of Xq27.1q28 duplicates spanning 14.45 Mb, which was inherited from a mild phenotype mother. Neither the father nor the mother\'s younger brother carried this duplication.
CONCLUSIONS: In this study, we examined a male child in a family who exhibited developmental delay and recurrent respiratory tract infections as the main symptoms. We conducted thorough family investigations and genetic testing to determine the underlying causes of the disease. Our findings will aid in early diagnosis, genetic counseling for male patients in this family, as well as providing prenatal diagnosis and reproductive guidance for female carriers.
METHODS: Conventional G-banding was employed to analyze the chromosome karyotypes of all pedigrees under investigation. Subsequently, whole exome sequencing (WES), advanced biological information analysis, and pedigree validation were conducted, which were further confirmed by copy number variation sequencing (CNV-seq).
RESULTS: Chromosome karyotype analysis revealed that a male patient had a chromosome karyotype of 46,Y,dup(X)(q27.2q28). Whole-exon duplication in the MECP2 gene was revealed through WES results. CNV-seq validation confirmed the presence of Xq27.1q28 duplicates spanning 14.45 Mb, which was inherited from a mild phenotype mother. Neither the father nor the mother\'s younger brother carried this duplication.
CONCLUSIONS: In this study, we examined a male child in a family who exhibited developmental delay and recurrent respiratory tract infections as the main symptoms. We conducted thorough family investigations and genetic testing to determine the underlying causes of the disease. Our findings will aid in early diagnosis, genetic counseling for male patients in this family, as well as providing prenatal diagnosis and reproductive guidance for female carriers.
摘要：
背景：MECP2重复综合征（MDS）是一种罕见的X连锁基因组疾病，主要影响男性。它的特点是言语发育延迟或缺失，严重的运动和认知障碍，和反复呼吸道感染。MDS是由位于染色体Xq28上的染色体区域的重复引起的，该染色体区域包含甲基CpG结合蛋白2（MECP2）基因。MECP2作为转录抑制因子或激活因子，调节与神经系统发育相关的基因。这项研究的目的是提供MDS的临床描述，包括从胎儿期到新生儿期观察到的影像学变化。
方法：采用常规G显带分析所调查的所有家系的染色体核型。随后，全外显子组测序（WES），先进的生物信息分析，并进行了谱系验证，通过拷贝数变异测序(CNV-seq)进一步证实。
结果：染色体核型分析显示，一名男性患者的染色体核型为46，Y，dup（X）（q27.2q28）。通过WES结果揭示了MECP2基因中的全外显子重复。CNV-seq验证证实存在跨越14.45Mb的Xq27.1q28重复，遗传自轻度表型母亲。父亲和母亲的弟弟都没有重复。
结论：在这项研究中，我们检查了一个家庭中表现出发育迟缓和反复呼吸道感染为主要症状的男性儿童。我们进行了彻底的家庭调查和基因检测，以确定疾病的根本原因。我们的发现将有助于早期诊断，为这个家庭的男性患者提供遗传咨询，以及为女性携带者提供产前诊断和生殖指导。
方法：采用常规G显带分析所调查的所有家系的染色体核型。随后，全外显子组测序（WES），先进的生物信息分析，并进行了谱系验证，通过拷贝数变异测序(CNV-seq)进一步证实。
结果：染色体核型分析显示，一名男性患者的染色体核型为46，Y，dup（X）（q27.2q28）。通过WES结果揭示了MECP2基因中的全外显子重复。CNV-seq验证证实存在跨越14.45Mb的Xq27.1q28重复，遗传自轻度表型母亲。父亲和母亲的弟弟都没有重复。
结论：在这项研究中，我们检查了一个家庭中表现出发育迟缓和反复呼吸道感染为主要症状的男性儿童。我们进行了彻底的家庭调查和基因检测，以确定疾病的根本原因。我们的发现将有助于早期诊断，为这个家庭的男性患者提供遗传咨询，以及为女性携带者提供产前诊断和生殖指导。
