PMC9705967_01
PMC9705967_02
Renal ultrasound findings of the patient. Ultrasound showed bilateral hypodysplastic kidneys with enhanced echogenicity and obtained corticomedullary differentiation. The size and thickness of left and right kidneys of the patient are as follows: (A) 3 months: 38 mm x 19 mm, 6.2 mm and 34 mm x 17 mm, 4.8 mm (reference range: 55.7-64.1 mm x 32.2-36.2 mm, 23.1-28.1 mm and 55.4-63.8 mm x 29.4-33.4 mm, 22.3-26.9 mm); (B) 5 months: 38 mm x 22 mm, 8.1 mm and 36 mm x 17 mm, 6.4 mm (reference range: 55.7-64.1 mm x 32.2-36.2 mm, 23.1-28.1 mm and 55.4-63.8 mm x 29.4-33.4 mm, 22.3-26.9 mm); (C) 6 months: 43 mm x 24 mm, 7.4 mm and 41 mm x 21 mm, 8.0 mm (reference range: 55.7-64.1 mm x 32.2-36.2 mm, 23.1-28.1 mm and 55.4-63.8 mm x 29.4-33.4 mm, 22.3-26.9 mm); (D) 9 months: 45 mm x 25 mm, 7.4 mm and 43 mm x 21 mm, 7.6 mm (reference range: 62.3-67.3 mm x 34.2-37.2 mm, 24.9-29.7 mm and 61.6-67.4 mm x 33.7-37.3 mm, 23.7-30.1 mm); (E) 1 year: 41 mm x 19 mm, 8.1 mm and 42 mm x 18 mm, 6.8 mm (reference range: 62.3-67.3 mm x 34.2-37.2 mm, 24.9-29.7 mm and 61.6-67.4 mm x 33.7-37.3 mm, 23.7-30.1 mm); (F) 1 year and 4 months: 40 mm x 19 mm, 6.1 mm and 41 mm x 19 mm, 6.5 mm (reference range: 62.3-67.3 mm x 34.2-37.2 mm, 24.9-29.7 mm and 61.6-67.4 mm x 33.7-37.3 mm, 23.7-30.1 mm).
fped-10-1020536-g002.jpg
PMC9705967_02_fped-10-1020536-g002.jpg
F2
Abdominal ultrasound revealed bilateral hypodysplastic kidneys (Figure 2).
Genetic test results. (A,B) Sanger sequencing of the targeted NOTCH2 variation in the proband's family members. The arrows indicate that the patient's parents possessed the wild-type genotype for NOTCH2. (C) Identification of a NOTCH2 pathogenic variant in the patient. The arrows indicate an alteration from A to G in the NOTCH2 gene of the patient. (D) Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.
fped-10-1020536-g003.jpg
PMC9705967_02_fped-10-1020536-g003.jpg
F3
Transcriptomic sequencing was used to verify the splice site change at the RNA level caused by the variant, thus confirming that the c.5930-2A > G variant could lead to the skipping of exon 33, thereby leading to alterations in NOTCH2 mRNA splicing (Figure 3).