| Background Due to high-throughput sequencing technology,chromosome microarray analysis(CMA)has rapidly expanded in the field of prenatal diagnosis.CMA has significant advantages in detecting congenital malformations and neurodevelopmental abnormalities,and has detected many copy number variations(CNV)of hereditary or new mutations.Chromosome 16 contains many low copy repeats(LCRs),and the complex structure of the p-arm indicates that it is a candidate region for new microduplication and microdeletion syndromes.16p13.11 belongs to the nervous susceptibility region,and the NDE1 gene is the strongest candidate gene for this segment.Research on 16p13.11 microduplication is scarce and reaching a consensus on its clinical manifestations is a challenge;most reports are of post-natal cases,not prenatal cases.Objectives This study aims to explore the genotype-phenotype correlation of16p13.11 microduplication,comprehensively analyze clinical and cytogenetics,and evaluate its pathogenicity in prenatal diagnosis,in order to provide help for genetic counseling.Methods Patients(n = 61)with neurocognitive impairment and patients(n = 6144)with other causes(i.e.,old age,abnormal results of non-invasive prenatal testing,microcephaly)who underwent CMA testing were reviewed and divided into three groups:(1)patient group with neurocognitive impairment;(2)prenatal group with abnormal nervous system;(3)prenatal group without abnormal nervous system.The fetuses with 16p13.11 microduplication were followed up with clinical phenotypes and the source of variation was verified.The detection rates of 16p13.11 microduplication in the three groups were statistically analyzed.Results No cases with 16p13.11 microduplication were detected in groups one and two;however,in group three,13 fetuses carrying 16p13.11 microduplication were detected,with the fragment range of chr16: 14892975–18172468,containing all NDE1 genes.Among them,one pregnancy was terminated due to fetal cardiac abnormalities.The pregnancies of cases 1–12 continued and no abnormalities were found in the prenatal examination of the fetuses.Follow-up examinations after birth(cases 1–10)also detected no obvious abnormalities.Among the 13 fetuses,the results showed that one case was a new mutation and two cases were inherited from a mother with normal clinical phenotype.In addition,there was no statistically significant difference in the detection rate of 16p13.11 microduplication cases among the three groups(p>0.05).Conclusions Fetuses with 16p13.11 microduplicates were found to have no abnormal clinical phenotype during postnatal follow-up.Therefore,16p13.11 microduplication containing mutation of the NDE1 gene may be benign.However,a larger study is needed to evaluate the relevant clinical phenotype.For prenatal cases with 16p13.11 microduplication,follow-up to adulthood is recommended. |
