case_images: PMC5041540_01
case_images: Facial and whole body photographs of two affected children in our study. a, b Proband 1 at age of 4 years and 8 months has cupped ears as well as a unilateral ear pit in her right ear. c Proband 1 at age of 4 years and 8 months shows similar length with her younger brother, proband 2 at 2 years and 2 months. d, e Proband 2 at age of 2 years and 2 months has mild craniofacial dysmorphisms with bilateral epicanthal folds and periorbital swelling
case_images: 13039_2016_286_Fig1_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig1_HTML.jpg
case_images: Fig1
case_images: In the developmental test performed at the age of 2 years, he demonstrated severe delays across all areas consistent with overall cognitive and motor impairment as well as craniofacial dysmorphisms with bilateral epicanthal folds and periorbital swelling (Fig. 1d, e).
case_images: The relevant section of copy number variants (CNVs) by array comparative genomic hybridization with the use of Agilent 244 K arrays. Please note that the coordinates shown in Fig. 2 are based on NCBI36/hg18 of the Human Genome Browser, which were translated into GRCh37/hg19 in the Case Presentation section. a 1q21 deletion in proband 1. b 7q11.22 deletion in proband 1. c Xq28 duplication in proband 2. On the scale of deviation from the normal diploid genotype, -2 indicates a homozygous deletion, -1 indicates a haploid deletion, 0 indicates no deviation, 1 indicates a duplication, and 2 indicates a triplication. X axis indicates the location of CNVs on chromosomes (hg18)
case_images: 13039_2016_286_Fig2_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig2_HTML.jpg
case_images: Fig2
case_images: A CGH array result demonstrated that proband 2 has 508 Kb duplication at Xq28 with the genome coordinates from 153,101,077 to 153,609,163 (GRCh37/hg19) encompassing 15 genes including MECP2, one of responsible genes for Xq28 duplication syndrome (Figs. 2c and 3c, Table 2). Figure 4d shows proband 2 has almost double amount of MECP2 mRNA expression compared to other family members.
case_images: Genome view of deletion and duplication regions in proband 1 (a and b) and 2 (c) exported from Human Genome Browser (Build 37/hg19). RefSeq genes are described in http://www.genome.ucsc.edu/. Black boxes under browser maps show approximate locations of loci where primers were designed for qPCR
case_images: 13039_2016_286_Fig3_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig3_HTML.jpg
case_images: Fig3
case_images: A CGH array result demonstrated that proband 2 has 508 Kb duplication at Xq28 with the genome coordinates from 153,101,077 to 153,609,163 (GRCh37/hg19) encompassing 15 genes including MECP2, one of responsible genes for Xq28 duplication syndrome (Figs. 2c and 3c, Table 2).
case_images: Quantitative PCR results of deletions and duplication in our family members. a qPCR results showing the 1q21 deletion using 2 different set of primers amplifying the regions within the known deleted region in proband 1. Deletion was detected only in proband 1. A value close to 0.5 indicates deletion on one chromosome 1, but a value close 1 indicates no deletion. b qPCR results showing the 7q11 deletion in both father and proband 1. Deletion in proband 1 was inherited from healthy father suggesting that this deletion is polymorphism. A value close to 0.5 indicates deletion on one chromosome 7, but a value close 1 indicates no deletion. c qPCR results showing duplication of Xq28 in proband 2, mother and MGM. Xq28 duplication in proband 2 is originally inherited from the maternal grandmother. Values indicate that: 1 (no deletion on chromosome X in male); 2 (duplication on chromosome X in male, no duplication in female); 3 (duplication on chromosome X in female). The amplification levels of GAPDH exon 8 were used to normalize relative levels of DNA. d The mRNA expression levels of MECP2 in the family members. Quantitative RT-PCR was performed to measure the mRNA levels of MECP2 using 2 different sets of primers specific to MECP2 mRNA (NM_004992.3). Expression of GAPDH was used to normalize relative expression of MECP2 mRNA. Error bars represent standard errors. Proband 1: a 10-year old Caucasian female with 1q21 microdeletion; Proband 2: an 8-year old Caucasian male with Xq28 duplication; MGF: maternal grandfather; MGM: maternal grandmother
case_images: 13039_2016_286_Fig4_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig4_HTML.jpg
case_images: Fig4
case_images: The qPCR results using two different primers amplifying regions within the known duplicated region revealed that Xq28 duplication was originally inherited from maternal grandmother who inherited it to mother, a carrier with a normal phenotype (Fig. 4c). Figure 4d shows proband 2 has almost double amount of MECP2 mRNA expression compared to other family members.
case_images: PMC5041540_02
case_images: Facial and whole body photographs of two affected children in our study. a, b Proband 1 at age of 4 years and 8 months has cupped ears as well as a unilateral ear pit in her right ear. c Proband 1 at age of 4 years and 8 months shows similar length with her younger brother, proband 2 at 2 years and 2 months. d, e Proband 2 at age of 2 years and 2 months has mild craniofacial dysmorphisms with bilateral epicanthal folds and periorbital swelling
case_images: 13039_2016_286_Fig1_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig1_HTML.jpg
case_images: Fig1
case_images: In the developmental test performed at the age of 2 years, he demonstrated severe delays across all areas consistent with overall cognitive and motor impairment as well as craniofacial dysmorphisms with bilateral epicanthal folds and periorbital swelling (Fig. 1d, e).
case_images: The relevant section of copy number variants (CNVs) by array comparative genomic hybridization with the use of Agilent 244 K arrays. Please note that the coordinates shown in Fig. 2 are based on NCBI36/hg18 of the Human Genome Browser, which were translated into GRCh37/hg19 in the Case Presentation section. a 1q21 deletion in proband 1. b 7q11.22 deletion in proband 1. c Xq28 duplication in proband 2. On the scale of deviation from the normal diploid genotype, -2 indicates a homozygous deletion, -1 indicates a haploid deletion, 0 indicates no deviation, 1 indicates a duplication, and 2 indicates a triplication. X axis indicates the location of CNVs on chromosomes (hg18)
case_images: 13039_2016_286_Fig2_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig2_HTML.jpg
case_images: Fig2
case_images: A CGH array result demonstrated that proband 2 has 508 Kb duplication at Xq28 with the genome coordinates from 153,101,077 to 153,609,163 (GRCh37/hg19) encompassing 15 genes including MECP2, one of responsible genes for Xq28 duplication syndrome (Figs. 2c and 3c, Table 2). Figure 4d shows proband 2 has almost double amount of MECP2 mRNA expression compared to other family members.
case_images: Genome view of deletion and duplication regions in proband 1 (a and b) and 2 (c) exported from Human Genome Browser (Build 37/hg19). RefSeq genes are described in http://www.genome.ucsc.edu/. Black boxes under browser maps show approximate locations of loci where primers were designed for qPCR
case_images: 13039_2016_286_Fig3_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig3_HTML.jpg
case_images: Fig3
case_images: A CGH array result demonstrated that proband 2 has 508 Kb duplication at Xq28 with the genome coordinates from 153,101,077 to 153,609,163 (GRCh37/hg19) encompassing 15 genes including MECP2, one of responsible genes for Xq28 duplication syndrome (Figs. 2c and 3c, Table 2).
case_images: Quantitative PCR results of deletions and duplication in our family members. a qPCR results showing the 1q21 deletion using 2 different set of primers amplifying the regions within the known deleted region in proband 1. Deletion was detected only in proband 1. A value close to 0.5 indicates deletion on one chromosome 1, but a value close 1 indicates no deletion. b qPCR results showing the 7q11 deletion in both father and proband 1. Deletion in proband 1 was inherited from healthy father suggesting that this deletion is polymorphism. A value close to 0.5 indicates deletion on one chromosome 7, but a value close 1 indicates no deletion. c qPCR results showing duplication of Xq28 in proband 2, mother and MGM. Xq28 duplication in proband 2 is originally inherited from the maternal grandmother. Values indicate that: 1 (no deletion on chromosome X in male); 2 (duplication on chromosome X in male, no duplication in female); 3 (duplication on chromosome X in female). The amplification levels of GAPDH exon 8 were used to normalize relative levels of DNA. d The mRNA expression levels of MECP2 in the family members. Quantitative RT-PCR was performed to measure the mRNA levels of MECP2 using 2 different sets of primers specific to MECP2 mRNA (NM_004992.3). Expression of GAPDH was used to normalize relative expression of MECP2 mRNA. Error bars represent standard errors. Proband 1: a 10-year old Caucasian female with 1q21 microdeletion; Proband 2: an 8-year old Caucasian male with Xq28 duplication; MGF: maternal grandfather; MGM: maternal grandmother
case_images: 13039_2016_286_Fig4_HTML.jpg
case_images: PMC5041540_02_13039_2016_286_Fig4_HTML.jpg
case_images: Fig4
case_images: The qPCR results using two different primers amplifying regions within the known duplicated region revealed that Xq28 duplication was originally inherited from maternal grandmother who inherited it to mother, a carrier with a normal phenotype (Fig. 4c). Figure 4d shows proband 2 has almost double amount of MECP2 mRNA expression compared to other family members.