case_images: PMC11772432_01
case_images: The pedigree information of the family and ultrasound examination results in the present fetus. (A) The pedigree analysis results of the enrolled family. The arrow indicates the proband. (B) Ultrasound examination results revealed short limbs and curved bones. (C) A narrow chest was also observed in the fetus. In addition, enhanced renal echogenicity (D,E) and oligohydramnios (F) was observed in the present fetus.
case_images: fped-12-1503455-g001.jpg
case_images: PMC11772432_01_fped-12-1503455-g001.jpg
case_images: F1
case_images: This is her fourth pregnancy and several ultrasound anomalies were detected including short limbs, curved bones, narrow chest, enhanced renal echogenicity, oligohydramnios, enhanced intestinal echogenicity, and choroid plexus cyst (Figure 1).
case_images: A 14.38-kb novel deletion compound with a missense variant in WDR35 is identified in the fetus. (A) Trio-whole exome sequencing (trio-WES) demonstrated a missense variant NM_001006657.2:c.932G>T(p.W311l) in WDR35 in the fetus. (B) Sanger sequencing verified the c.932G>T in the fetus, which was also present in the mother. (C) A 14.38-kb deletion compound encompassing exon 7 to exon 12 was also identified in the fetus using trio-WES. (D) qPCR analysis revealed a heterozygous deletion from exon 7 to exon 12 in WDR35 in both the fetus and the father, but the fetus's mother did not have the deletion.
case_images: fped-12-1503455-g002.jpg
case_images: PMC11772432_01_fped-12-1503455-g002.jpg
case_images: F2
case_images: According to the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were supposed to be pathogenic, which was further confirmed by Sanger sequencing and real time quantitative PCR (qPCR) (Figure 2).
case_images: Two compounded heterozygous variants in NPHP4 gene were identified in the fetus. (A,C) Trio-WES demonstrated an NM_015102.5:c.1196A>G(p.E399G) compounded with NM_015102.5:c.1972C>T(p.R658*) in NPHP4 gene in the fetus, which was inherited from the parents, respectively. (B,D) Sanger sequencing verified both of the variants in the family.
case_images: fped-12-1503455-g003.jpg
case_images: PMC11772432_01_fped-12-1503455-g003.jpg
case_images: F3
case_images: Both variants were further verified by Sanger sequencing (Figure 3).