case_images: PMC11749679_01
case_images: Prenatal ultrasound image and growth curve of the fetus at 25 weeks of gestation. The chart depicts the growth trajectories of head circumference and BPD throughout pregnancy including the standard growth curve along with plus and minus 2 SDs, which serve as a means to identify potential abnormalities in fetal growth and development. (A) The prenatal ultrasound at 25 weeks revealed a BPD of 4.79 cm and an HC of 17.9 cm. (B) The growth curve for BPD showed that at 25 weeks of gestation, the fetal BPD was 4.41 SDs below average. (C) The growth curve for HC indicated that at 25 weeks of gestation, the fetal HC was 5.02 SDs below average. BPD = biparietal diameter, HC = head circumference, SDs = standard deviations.
case_images: medi-104-e41300-g001.jpg
case_images: PMC11749679_01_medi-104-e41300-g001.jpg
case_images: F1
case_images: In contrast, the fetal femur length was 4.3 cm, falling within the normal range (Fig. 1).
case_images: Whole-exome sequencing results. (A) The fetus and the patient's husband carried the PNKP c.976G > A mutation (II:5, III:3). (B) The fetus and the patient carried the PNKP c.1188G > A mutation (II:6, III:3). PNKP = polynucleotide kinase 3'-phosphatase.
case_images: medi-104-e41300-g002.jpg
case_images: PMC11749679_01_medi-104-e41300-g002.jpg
case_images: F2
case_images: The patient carried the PNKP c.1188 + 1G > A mutation, and her current husband carried the PNKP c.976G > A (p.E326K) mutation (Fig. 2).
case_images: Three splice patterns of PNKP (NM_007254.4, c.1188 + 1G > A). PNKP = polynucleotide kinase 3'-phosphatase.
case_images: medi-104-e41300-g003.jpg
case_images: PMC11749679_01_medi-104-e41300-g003.jpg
case_images: F3
case_images: This variant is associated with 3 splice patterns: (1) the insertion of 62 bp leading to alternative splicing donors, frameshift mutation, and premature termination; (2) the deletion of 62 bp resulting in exon skipping, frameshift mutation, and premature termination; and (3) the insertion of 162 bp causing intron retention and premature termination (Fig. 3).
case_images: Core pedigree chart. The fetus had compound heterozygous PNKP mutations c.976G > A (p.E326K) and c.1188 + 1G > A (III:3). The patient and her daughter from a previous marriage carried the PNKP c.1188 + 1G > A mutation (II:6, III:5). TOP 25wks: Termination of pregnancy at 25 weeks (III:4). The patient's current husband, his father, and his daughter from a previous marriage carried the PNKP c.976G > A mutation (I:1, II:5, III:2). (-): Negative for PNKP gene mutation (II:1, II:3, III:1). E = glutamic acid, K = lysine, PNKP = polynucleotide kinase 3'-phosphatase.
case_images: medi-104-e41300-g004.jpg
case_images: PMC11749679_01_medi-104-e41300-g004.jpg
case_images: F4
case_images: Notably, neither the husband's 2 sisters nor his nephew carried the PNKP gene mutation (Figs. 4 and 5).
case_images: Results of molecular genetic testing for monogenic disease: PNKP c.976G > A (p.E326K) and PNKP c.1188 + 1G > A. E = glutamic acid, K = lysine, PNKP = polynucleotide kinase 3'-phosphatase.
case_images: medi-104-e41300-g005.jpg
case_images: PMC11749679_01_medi-104-e41300-g005.jpg
case_images: F5
case_images: Notably, neither the husband's 2 sisters nor his nephew carried the PNKP gene mutation (Figs. 4 and 5).
case_images: 3D protein modeling of PNKP missense variants p.E326K. The E326K protein mutation causes changes in charge and interactions, leading to alterations in protein function. Protein 3D molecular modeling was predicted by AlphaFold2.3.0 software. E = glutamic acid, K = lysine, PNKP = polynucleotide kinase 3'-phosphatase.
case_images: medi-104-e41300-g006.jpg
case_images: PMC11749679_01_medi-104-e41300-g006.jpg
case_images: F6
case_images: The mutated K326 site forms hydrogen bonds with K330 and T323, with bond distances of 3.4, 3.4, and 3.2 A. This mutation modifies the charge properties and interactions of the side chain, ultimately resulting in functional changes (Fig. 6).