ATP7A Gene Mutation Analysis And Prenatal Diagnosis Of Five Pedigree With Menkes Disease

Objective:In this study the karyotype of ATP7 A of 5 Menkes disease families were analyzed through the next-generation sequencing,by which we identified the mutation in the context of challenging genetic counselling and prenatal diagnosis situation.Method:Mutation analysis of ATP7 A was carried by polymerase chain reaction(PCR)and the next-generation sequencing so that the mutation spot had been identified and the genetic diagnosis confirmed. Then on the basis of the ATP7 Amutations in 5 cases, three G2P2A0 mothers from family 1,3 and 5 taken the amniocentesis at the 18th~20thweek of pregnancy respectively, and villus biopsy was conducted on the other two G2P2A0 mothersat the 9th~12thweek of pregnancy. Genomic DNA of the infants had been isolated so that the gender of the infants was identified,also the biological parents,the maternal blood status and the ATP7 A mutation analysis.Results:The mutation ATP7 A of the proband was identified as point mutation,c.2179G>A(p.G727R) for family1 and family 2,c.3914A>G(p.D1305G) for family3,c.1642G>T(p.Glu548*) for family 4 and c.3905G>A(p.G1302E) for family 5.The mutation of mothers of family 1,2 and 5 was identified as heterozygosis, either the elder sister of the proband of family 5 at the same site.Among the infants except family 2 the others all were identified as male. The DNA sequencing showed that the karyotype of theinfants of family 1-4 were wild type,the other one was identified as point mutation at the same site as the proband.Conclusions:In this study the karyotype of ATP7 A of 5 Menkes disease families were analyzed, by which we identified previously unreported mutations c.1642G>T( p.Glu548*) and c.3905G>A(p.G1302E)and the ATP7 A mutation female carriers in the family were confirmed in the context of challenging genetic counselling and prenatal diagnosis situation.