De novo MECP2 duplication derived from paternal germ line result in dysmorphism and developmental delay |
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| Authors: | Dar-Shong Lin Tzu-Po Chuang Ming-Fu Chiang Che-Sheng Ho Chung-Der Hsiao Yu-Wen Huang Tsu-Yen Wu Jer-Yuarn Wu Yuan-Tsong Chen Tsai-Chuan Chen Ling-Hui Li |
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| Affiliation: | 1. Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan;2. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;3. Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan;4. Molecular Medicine Program, Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;5. Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan;6. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;g Department of Pediatrics, Duke University Medical Center, Durham, USA;h Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan;i Department of Bioscience Technology, Chung Yuan Christian University, Chung Li, Taiwan;j Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan;k Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan |
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| Abstract: | Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males exhibit a distinct phenotype, including developmental delay, facial dysmorphism, muscular hypotonia, intellectual disability, poor or absent speech, recurrent infections and early death. The vast majority of affected males inherit the MECP2 duplication from their usually asymptomatic carrier mothers. Only a few cases with Xq28 duplication originating from de novo unbalanced X/Y translocation have been reported and the paternal origin of the aberration has only been validated in three males in the related literature. Here we present a karyotypically normal male with features characteristic of the MECP2 duplication syndrome. The genome-wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the terminus. The genotypes of the SNPs within the duplicated region indicated a paternal origin. Furthermore, the results of fluorescence in situ hybridization (FISH) indicated a novel Xq:Yp translocation, characterized as der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during spermatogenesis. The phenotype is compared to the previously reported cases with Xq28 duplication originated from an unbalanced X/Y translocation, and there was no specific part of the phenotype that could be contributed to the origin of parental imbalances. This report further highlights the capacity of high-molecular cytogenetic methods, such as SNP array and FISH, in the identification of submicroscopic rearrangement, structural configuration and parental origin of aberrant while in the evaluation of children with idiopathic developmental delay and intellectual disability. |
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| Keywords: | MECP2, methyl CpG binding protein 2 FISH, fluorescence in situ hybridization SNP, single-nucleotide polymorphism CGH, comparative genome hybridization CNVs, copy number variations FoSTeS, Fork Stalling and Template Switching IFN-α, interferon alpha |
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