Abstract
BACKGROUND: The 17q22 deletion syndrome is associated with a range of clinical phenotypes, primarily due to differences in the size and position of the deleted genomic segment. In all previously reported cases, diagnoses were made postnatally, with clinical manifestations such as intellectual disability, visual impairment, and other neurological abnormalities. METHODS: Karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing were performed to identify the genetic etiology of a fetus with nuchal pellucida thickening. Summarize the previously reported cases of similar 17q22 deletions and conduct a systematic review. RESULTS: Chromosomal microarray analysis revealed an arr[GRCh37] 17q22(55,501,204_56,476,808) × 1, which was confirmed as a de novo variant by whole-exome sequencing. Comprehensive prenatal sonography revealed multiple structural abnormalities in the fetus, including neurodevelopmental abnormalities and distinct craniofacial features. A comprehensive search uncovered 24 postnatal cases with 17q22 deletions overlapping our findings. All these cases showed consistent neurological abnormalities, further supporting the genotype-phenotype association. CONCLUSION: Integrating the genetic findings in this fetus, the abnormal ultrasound structural phenotype, and the clinical characteristics of existing cases, we conclude that SRSF1 haplotype deficiency is the fundamental genetic cause underlying the observed fetal ultrasound abnormalities. This report of the 17q22 deletion (include SRSF1) provides an essential reference for prenatal genetic counseling and phenotypic interpretation.