SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick diseasetype C

The molecular prenatal diagnosis of Niemann-Pick disease type C (NPC) is pr esented. The proband with a late infantile type of NPC was a compound heter ozygote of a paternal missense mutation, T529G, and a maternal 2 bp deletio n at nt 350 of the NPC1 gene. These mutations were detected by single-stran d conformation polymorphism (SSCP) analysis of RT-PCR products. When the pr oband was aged 4 years 3 months, prenatal diagnosis for the second child wa s performed using both biochemical and molecular methods. SSCP analysis for the parental mutations using cDNA from cultured amniotic fluid cells revea led the absence of both mutations and the fetus was diagnosed as being unaf fected. This diagnosis was supported by a normal level of cholesterol ester ification using cultured amniotic fluid cells. After the child's birth, whe n he was 21 months old, the diagnosis was confirmed by SSCP analysis of gen omic DNAs of his family. This analysis also revealed a unique variation of intron 13, IVS13 + 753-758 del TTTTTT, that was shared only by the proband and the father, and was suspected as bring linked to the T529G missense mut ation. A combination of both biochemical and molecular analyses is very use ful and reliable for prenatal diagnosis of Niemann-Pick disease type C. Cop yright (C) 2001 John Wiley & Sons, Ltd.