Prenatal detection of pure proximal 6q14.1 microduplication encompassing LCA5 gene: A variant of likely benign

Trisomy 6q is a recognizable syndrome which exhibits psychomotor/growth retardation, developmental/intellectual disabilities, feeding difficulties, facial dysmorphism, hearing loss, brain and heart malformations. The purpose of this study was to delineate the prenatal features of proximal 6q14.1 duplication in fetal period, which was rarely reported in clinic. Eight pregnant women who opted for amniocentesis due to the fetal ultrasound abnormalities, maternal serum screening or other indications for prenatal diagnosis between 2019 and 2020. Chromosomal microarray analysis and G-banding analysis were offered after informed consents were obtained. Cytogenetic prenatal investigation showed all fetuses presented normal karyotypes except case 4 exhibiting a balanced chromosomal translocation 46,XX,t (4;8)(p16;q24). The chromosomal microarray analysis detected 0.211–0.242 Mb duplications of 6q14.1 (chr6: 80109532–80351666, hg19) in all 8 cases, encompassing the morbid gene LCA5 in common. Seven pregnant women (P1-P7) continued their pregnancies and delivered healthy infants at term while the parents of case 8 opted for termination of pregnancy for severe abnormal ultrasound findings. Overall, all neonates were in a good healthy condition with no evident anomalies, ranging from 2 m to 16 m. It is proposed that 6q14.1 duplication involving LCA5 gene detected in our study might be variants of likely benign. However, further large-scale studies should be gathered to assess its pathogenicity. To our knowledge, our study is the first report focusing on prenatally detected proximal 6q14.1 duplication, accompanied by detailed clinic phenotypes. Diverse ultrasound findings were observed in these cases, ranging from normal to abnormal. More evidence should be gathered to interpret the prenatal genotype-phenotype correlation of 6q14.1 duplication. For these cases with 6q14.1 microduplication, long term follow up should be carried out in case abnormal clinical symptoms or developmental-behavioral disorders emerge.