case_images: PMC10277930_01
case_images: Brain magnetic resonance imaging (MRI), Sanger sequencing, and quantitative polymerase chain reaction (q-PCR). (A) Brain MRI of the patient at 8 months of age. T1: Cerebellar and brain stem hypoplasia with a characteristic flattening (red arrow). T2: Pachygyria-polymicrogyria of frontotemporal lobes (type "cobblestone pavement") (yellow arrows) and white matter lesions (white arrows). T2: Multiple subcortical cerebellar cysts (green arrows). (B) Sanger sequencing showed a homozygous c.636C>T variant in exon 7 of the POMGNT1 gene (NM_001243766) in the patient. His father had a heterozygous c.636C>T variant, and his mother had no variant in this site. (C) Q-PCR of DNA showed a normal copy number in exon 7 of POMGNT1 in the patient.
case_images: fgene-14-1170089-g001.jpg
case_images: PMC10277930_02_fgene-14-1170089-g001.jpg
case_images: F1
case_images: Sanger sequencing revealed that the father had a heterozygous c.636C>T variant, but the mother had no variant at this site (Figure 1B). However, no abnormalities were found (Figure 1C), suggesting that there may be another cause of the homozygous variant.
case_images: PMC10277930_02
case_images: Brain magnetic resonance imaging (MRI), Sanger sequencing, and quantitative polymerase chain reaction (q-PCR). (A) Brain MRI of the patient at 8 months of age. T1: Cerebellar and brain stem hypoplasia with a characteristic flattening (red arrow). T2: Pachygyria-polymicrogyria of frontotemporal lobes (type "cobblestone pavement") (yellow arrows) and white matter lesions (white arrows). T2: Multiple subcortical cerebellar cysts (green arrows). (B) Sanger sequencing showed a homozygous c.636C>T variant in exon 7 of the POMGNT1 gene (NM_001243766) in the patient. His father had a heterozygous c.636C>T variant, and his mother had no variant in this site. (C) Q-PCR of DNA showed a normal copy number in exon 7 of POMGNT1 in the patient.
case_images: fgene-14-1170089-g001.jpg
case_images: PMC10277930_02_fgene-14-1170089-g001.jpg
case_images: F1
case_images: Sanger sequencing revealed that the father had a heterozygous c.636C>T variant, but the mother had no variant at this site (Figure 1B). However, no abnormalities were found (Figure 1C), suggesting that there may be another cause of the homozygous variant.
case_images: Analysis of uniparental disomy (UPD) using trio-based whole-exome sequencing (trio-WES). It showed that paternal UPD existed on chromosome 1. UI_P: Uniparental Paternal Isodisomy. UA_P: Uniparental Paternal Heterdisomy. UI_M: Uniparental Maternal Isodisomy. UA_M: Uniparental Maternal Heterdisomy. BPI: Bi-Parental Inheritance. Het: Heterozygous. Hom: Homozygous.
case_images: fgene-14-1170089-g002.jpg
case_images: PMC10277930_02_fgene-14-1170089-g002.jpg
case_images: F2
case_images: As a result, a possible paternal UPD on chromosome 1 of the patient was identified using trio-WES data analysis (Figure 2), which revealed the homozygous variant, and no other pathogenic variants were detected.
case_images: Chromosomal microarray analysis (CMA) and RNA sequencing (RNA-seq). (A) CMA showed a 120,451 kb loss of heterozygosity (LOH) on 1p36.33-p11.2 (888,658_121,339,317) and a 99,319 kb LOH on 1q21.2-q44 (149,879,544_249,198,164). The former encompassed the POMGNT1 gene. (B) RNA-seq showed skipped exon 7 in the POMGNT1 mRNA of the patient and the father. RPKM: Reads Per Kilobase per Million mapped reads. IncLevel: Inclusion Level.
case_images: fgene-14-1170089-g003.jpg
case_images: PMC10277930_02_fgene-14-1170089-g003.jpg
case_images: F3
case_images: Finally, chromosomal microarray analysis (CMA) of the patient revealed a 120,451 kb loss of heterozygosity (LOH) on 1p36.33-p11.2 (888,658_121,339,317), encompassing POMGNT1, and a 99,319 kb LOH on 1q21.2-q44 (149,879,544_249,198,164) (Figure 3A). It was confirmed to cause the skipping of exon 7 in the POMGNT1 mRNA (Figure 3B), resulting in a frameshift change (p.Asp179Valfs*23).