Prenatal diagnosis and genetic counseling of fragile X syndrome in four pedigrees by using high-resolution multiplex polymerase chain reaction

Abstract

Objectives To provide prenatal diagnosis and genetic counseling for four athigh-risk pregnant women with a suspected family or personal history of fragile X syndrome (FXS) by genetic screening of fragile X mental retardation (FMR1) gene. Methods This study was conducted on four pregnant women (No.1 to 4) who received outpatient treatment in Peking University First Hospital from August 2014 to June 2016. Genomic DNA was extracted from peripheral blood samples of the pregnant women and six of their family members, four of which were suspected or confirmed FXS and the other two were FMR1 gene carriers. Amplide X kits were used to detect CGG repeat size in FMR1 gene. Two amniocytes and one chorionic villi samples were collected from three pregnant women to extract DNAs for FMR1 gene and karyotyping analyses. Results There were patients diagnosed with FXS in all the families by detecting CGG repeat numbers in FMR1 gene. The pregnant woman No.1 was a permutation carrier; No.2 carried normal FMR1 alleles while her brother had a mutation with over 20 CGG repeats in FMRI gene at chromosome X. No.3 and 4 were full mutation carriers with over 200 CGG repeats in FMR1 gene. After genetic counseling, No.3 decided to terminate the pregnancy due to abnormal fetal karyotype (47, XY,+21) and full mutation of FMR1 alleles. No.1 and 4 continued to pregnancy as their fetuses were normal in FMR1 alleles and karyotype. No.2 continued to pregnancy as her fetus was free of FXS risk. Conclusions Prenatal diagnosis and genetic counseling should be conducted on women at high-risk for FXS to avoid birth defects. People with a family history of FXS should be tested for FMR1 gene carrier status. Key words: Fragile X syndrome; Fragile X mental retardation protein; Polymerase chain reaction; Prenatal diagnosis; Genetic testing; Genetic counseling