Clinical Findings and Genetic Analysis of Patients with Copy Number Variants Involving 17p13.3 By Using a Single Nucleotide Polymorphism Array: A Single-Center Experience

Abstract Background 17p13.3 microdeletions or microduplications (collectively known as copy number variants or CNVs) have been described in association with individuals with neurodevelopmental disorders. While, studies on 17p13.3 CNVs in prenatal diagnosis are limited. This study aims to investigate the clinical significance of 17p13.3 CNVs with varied size and gene contents in prenatal and postnatal samples. Methods Eight cases with 17p13.3 CNVs out of 8806 samples that had been subjected to single nucleotide polymorphism array analysis were retrospectively analyzed, along with karyotype, clinical features, and follow-up. Results Eight cases with 17p13.3 CNVs consisted of five fetuses, one abortion embryo and two probands manifested severe congenital defects. The prenatal findings varied significantly for the five fetuses, including ultrasound abnormalities (n = 3), segmental deletions indicated with non-invasive prenatal testing (n = 1), and pregnant women with intellectual disability (n = 1). Of them, two and six harbored copy number gains and losses involving 17p13.3, respectively. The size of the detected 17p13.3 CNVs ranged from 576 kb to 5.7 Mb. Case 1 was diagnosed with 17p13.3 duplication syndrome, and cases 4, 6, and 7 with Miller–Dieker syndrome (MDS). Microdeletions of the 17p13.3 region in two cases (cases 5 and 8) involving YWHAE and CRK, sparing PAFAH1B1, were classified as pathogenic. Case 2 harbored a 576 Kb microduplication, encompassing YWHAE and CRK but not PAFAH1B1, which was of maternal origin and considered a variant of uncertain significance. Case 3 had one large duplication spanning the partial short arm, centromere, and partial long arm, and two deletions at 17p13.3p13.2 and 17q25.3, which karyotype was 46,XY,r(17)(p13q25). For five fetuses, only case 2 continued gestation and showed a good outcome; the others were subjected to termination of pregnancy. Conclusion The clinical findings of 17p13.3 microdeletions or microduplications varied among subjects, and 17p13.3 CNVs often differ in size and gene contents. Microdeletions or microduplications containing the typical MDS region, as well as the microdeletions involving YWHAE and CRK, could be classified as pathogenic. The clinical significance of small duplications including YWHAE and CRK but not PAFAH1B1 remains uncertain, for which parental testing and clinical heterogeneity should be considered in genetic counseling.