Fig 1.
Family 1 results with t(1;7) translocation.
A) Family 1 pedigree showing the proband with intellectual disability, psychomotor delay and epilepsy, as well as the non-affected mother and father. The t(1;7)(p36.1;q22) translocation is maternally inherited. B) Ideograms showing the normal and derivative (der) chromosomes (chr) 1 and 7 (not to scale). Genetic material from chr1 and chr7 is shown with a solid, orange and dotted, blue frame line, respectively. The approximate breakpoint positions on 1p36.1 and 7q22 are indicated by arrows. C) UPD7 analysis results from one of the informative microsatellite markers (D71824) in the affected proband and non-affected parents; by comparing the peak sizes between all family members, normal biparental inheritance was concluded. D) Quantitative Real-Time PCR results demonstrating the paternal inheritance of the chr3 duplication predicted from the structural variant analysis in the affected proband.
Fig 2.
Translocation junction sequences identified in each family.
Translocation junction sequences to the base-pair level as identified by mate-pair sequencing and verified by Sanger sequencing in A) family 1 with t(1;7)(p36.1;q22), B) family 2 with t(7;8)(q32;q24.13), C) family 3 with t(4;10)(q35;q11.2), and D) family 4 with t(1;20)(p35.3;q13.3). Translocation junction sequences (middle line) and matching reference sequences (top and bottom lines) are shown with a different colour depending on the chromosome involved (chr1-orange; chr4-purple; chr7-blue; chr8-red; chr10-yellow; chr20-green). Microhomology observed at the translocation breakpoint sites is highlighted in yellow, deleted sequences around the breakpoints are underlined, duplicated sequences are in bold, capital letters, and inserted sequences not aligning to either chromosome are in bold, lower-case letters.
Table 1.
Breakpoint mapping and sequencing results for each apparently balanced translocation case included in this study.
Fig 3.
The ZNF423 gene and quantitative Real-Time PCR (qRT-PCR) results.
A) Schematic illustration of the ZNF423 gene (minus strand). The protein-coding exons and introns of the gene are represented with solid, vertical lines and dotted, horizontal lines, respectively (not to scale). Intron 3 is enlarged to demonstrate the approximate ZNF423 deletion position (blue line) as predicted by MPS in the affected sibling in family 2, as well as the amplicon (Z-RT1, Z-RT2, and Z-RT3) positions (red lines) from the qRT-PCR analysis. The actual coordinates are given on the left (GRCh37/hg19). B) qRT-PCR results demonstrating a reduced relative ZNF423 copy number in the proband and normal results in the non-affected sibling as compared with a control. Parental genomic material was unavailable and thus not included in the analysis.