case_images: PMC10619901_01
case_images: Whole paternal isodisomy (isoUPD) of chromosome 7. (A) ChAS revealed a complete regions of homozygosity (ROH) across the whole chromosome (purple rectangle, blue arrow). (B) A whole chromosome view clearly shows the copy-neutral ROH on chromosome 7 in the proband (red arrow). (C) ChAS software directly indicates that the UPD originated from his father after comparing the genotyping results between the proband and his parents (red arrows). (D) Classification of UPD using the UPDtool showed the proband was whole paternal isoUPD. FracHom (blue line) is the fraction of homozygous SNPs, FracME (red line) is the fraction of mendelian error SNPs, FracldentFather (green line) is the fraction of SNPs where the genotype is identical to the father, FracldentMother (black line) is the fraction of SNPs where the genotype is identical to the mother, and FracError (yellow line) is the fraction of errors. The UPDtool is available at: (http://www.unituebingen.de/uni/thk/de/f-genomik-software.html).
case_images: fgene-14-1272028-g001.jpg
case_images: PMC10619901_01_fgene-14-1272028-g001.jpg
case_images: F1
case_images: Evaluating uncultured amniocytes using an Affymetrix CytoScan 750 K SNP array did not detect pathogenic copy number variants and revealed regions of homozygosity on chromosome 7 (Figures 1A, B). Analysis Suite (ChAS) software (Figure 1C) and UPDtool (Figure 1D). After genetic counseling, we performed WES on the uncultured amniocytes.
case_images: Pedigree of the family and the Sanger sequencing data. (A) Family pedigree. The arrows indicate the proband. (B) Sanger sequencing showed a homozygous frameshift mutation on SUGCT (c.286delC) in the proband, while the father is heterozygous and his mother is normal.
case_images: fgene-14-1272028-g002.jpg
case_images: PMC10619901_01_fgene-14-1272028-g002.jpg
case_images: F2
case_images: We verified this result using Sanger sequencing; the mutation was inherited only from the father, who was heterozygous for this mutation (Figure 2).
case_images: The weight curve of the proband. (A) The trend of increasing weight with age of the proband. (B) The trend of increasing weight with length of the proband, according to the industry standard of the People's Republic of China (WS/T 423-2022), from birth to age 24 months.
case_images: fgene-14-1272028-g003.jpg
case_images: PMC10619901_01_fgene-14-1272028-g003.jpg
case_images: F3
case_images: The length and head circumference (data not shown) were within the normal range while weight was over 3SD from 6 months of age (Figure 3).