| OBJECTIVE1.Analyze the application value of Chromosome Microarray Analysis(CMA)in prenatal genetic diagnosis.2.Analyze the change in the nature of copy number variation of 15q11.2BP1-BP2 fragment found in CMA.METHODS1.To retrospectively analyze the abnormal detection of all prenatal diagnosis cases detected by CMA at the Prenatal Diagnostic Center of Nanjing Drum Hospital from June 1,2014 to December 31,2017.2.Fluorescence quantitative PCR(FQ-PCR)method was used to analyze the parental traceability of the fetuses with VOUS.3.Telephone follow-up of all fetuses'pregnancy outcomes and postnatal growth and development,genotypes and prenatal and postnatal phenotypes were analyzed.4.Combine the Gesell scale,the neuropsychological development scale for children from 0 to 6 years old,and the Wechsler Adult Intelligence Scale for intelligence psychoanalysis of carriers and parents.The nature of the 15q11.2BP1-BP2 copy number duplication in the assay was investigated.RESULTS1.Among the 1932 prenatally diagnosed fetuses,CMA showed no abnormalities in 1533 cases(79.35%),pathological variation in 238 cases(12.32%),of which aneuploidy abnormalities accounted for 4.97%,pathological CNV accounted for 7.35%,and VOUS was 161 cases(8.33%).The phenotypes of pathological CNV detection rate from high to low were:fetal growth retardation 10.74%(16/149), nervous system abnormality 9.25%(26/281),other structural abnormalities9.17%(20/218),urinary system abnormality 8.00%(10/125),nuchal translucency(NT)thicken7.89%(22/279),cardiovascularsystemabnormalities6.73%(23/342),skeletal system abnormalities 5.63%(12/213),digestive system abnormalities5.45%(3/55),non-structuralabnormalities3.77%(10/265),respiratory system abnormalities 0.2.With the consent of the parents,79 cases of CMA prompted VOUS fetuses and their parents to verify the source of copy number variation,72 cases of CNV were inherited from parents without abnormal phenotype,and 7 cases were new mutations.3.Follow-up was performed on 1932 prenatally diagnosed fetuses,and 328 patients were lost follow-up.The success rate was 83.02%.Of the 1604 fetuses that were effectively followed up,357 had induced labor and 1247 had live births.Among the 1247 newborns,1116(89.49%)had no abnormalities in CMA,15(1.20%)had pathological variation,and 116(9.30%)had VOUS.Among the 1116neonates with no abnormalities in CMA,1097(98.30%)had normal growth and development,and 19(1.70%)died of pathological causes or growth retardation after birth.Among the 15 live births of CMA who indicated pathological variation,1 case had uremia associated with chromosomal abnormalities,and 14cases were noamal.Among the 116 live births of CMA who indicated VOUS,62of the newborns had CNV from their parents,and their growth and development were normal;4 newborns were new mutations and no abnormalities;50newborns without parental traceability,49 cases had normal growth and development,1 case of prenatal ultrasound showed 29~+weeks of pregnancy,long boneswereshort(about4weeksbehind),CMAwas9p23(11,807,349-13,242,041)x3,and the diagnosis was"Pierre Pierre Robin"after birth,with a small jaw and a split.4.FQ-PCR results of 17 fetuses with 15q11.2 BP1-BP2 CNV carrying parental variation and their parents'samples suggested that 2 cases were new mutations(1 case carried microduplication,1 case carried microdeletion),and the remaining 15 cases of copy number variation were from parental inheritance(4 cases of microdeletions inherited from mother,5 cases of microdeletions inherited from father,2 cases of microduplication inherited from father,and 4 cases of microduplication inherited from mother).Seventeen patients with the copy number variation were followed up,one was lost follow-up,and 16 patients were followed up effectively.Of the 16 fetuses that were successfully followed up,7 were induced to give birth,and 9 fetuses were born.By the date of follow-up,the maximum was 39 months old,the minimum was 7 months old,the growth and exercise spirits met the reference standard.Fetal parents of 17 cases with copy number variation also had no abnormalities.CONCLUSIONIn this study,CMA can detect 7.35%more abnormalities in the field of prenatal diagnosis than traditional karyotype analysis techniques.The abnormal pathological CNV detection rate of each system is more than 5%,indicating that CMA can be used as a means of detecting abnormal fetal structures.VOUS is more likely benign variation,and the genotype-phenotype relationship is still unclear.Parental parental traceability,high-quality follow-up,and prenatal phenotype-genotype database accumulation can help with prenatal counseling.There was still 1.70%abnormality after birth which CMA showed no abnormality.Due to the uncertainty of fetal phenotype,full communication should be made during prenatal diagnosis and consultation.The pathogenicity level of the 15q11.2 BP1-BP2 copy number variation is gradually reduced.When consulting CNV,you should consult the database and the latest literature and verify the source of the source to provide patients with the latest genotype-phenotype correlation information. |
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