[Clinical features and genetic etiology analysis in a patient with Fliedner-Zweier syndrome caused by a de novo SCAF4 variant].

OBJECTIVE

To explore the clinical characteristics and genetic etiology of a patient with Fliedner-Zweier syndrome (FZS).

METHODS

A pregnant woman who was diagnosed with FZS at the Affiliated Women and Children's Hospital of Ningbo University in November 2023 for "intellectual disability, epilepsy, delayed language development and facial abnormalities" was selected as the study subject. Peripheral blood samples were collected from the woman and her husband, whilst amniotic fluid sample was obtained from the fetus. Following extraction of genomic DNA, whole-exome sequencing (WES) and chromosomal karyotyping analysis were performed. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094).

RESULTS

The proband, a 23-year-old woman, was at 19+2 weeks of gestation and had a history of epilepsy, mild intellectual disability, delayed language development, and subtle facial dysmorphism. Chromosomal analysis showed the she has a normal karyotype. WES revealed that the woman and her fetus both harbored a heterozygous c.1489C>T (p.Gln497Ter) nonsense variant of the SCAF4 gene, which was verified by Sanger sequencing as de novo. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_supporting+PS2_supporting). According to pre-set search strategy, five articles were retrieved. Together with the patient in this study, a total of 69 FZS patients were involved (including 7 from China). The main clinical features have included intellectual disability, epilepsy, behavioral abnormalities, and facial dysmorphism.

CONCLUSION

The heterozygous c.1489C>T (p.Gln497Ter) variant of the SCAF4 gene probably underlyay the FZS in this patient. Above finding has expanded the mutational spectrum of the SCAF4 gene.