PMC5041540_01
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
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PMC5041540_02_13039_2016_286_Fig1_HTML.jpg
Fig1
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).
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)
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PMC5041540_02_13039_2016_286_Fig2_HTML.jpg
Fig2
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.
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
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PMC5041540_02_13039_2016_286_Fig3_HTML.jpg
Fig3
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).
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
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PMC5041540_02_13039_2016_286_Fig4_HTML.jpg
Fig4
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.
PMC5041540_02
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
13039_2016_286_Fig1_HTML.jpg
PMC5041540_02_13039_2016_286_Fig1_HTML.jpg
Fig1
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).
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)
13039_2016_286_Fig2_HTML.jpg
PMC5041540_02_13039_2016_286_Fig2_HTML.jpg
Fig2
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.
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
13039_2016_286_Fig3_HTML.jpg
PMC5041540_02_13039_2016_286_Fig3_HTML.jpg
Fig3
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).
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
13039_2016_286_Fig4_HTML.jpg
PMC5041540_02_13039_2016_286_Fig4_HTML.jpg
Fig4
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.