Prenatal diagnosis of PLP1 copy number by array comparative genomic hybridization

Objectives To report a family with a history of Pelizaeus–Merzbacher disease (PMD) for which prenatal diagnosis of PLP1 gene duplication status was attempted by the use of custom array comparative genomic hybridization (aCGH). Methods A 28-year-old woman was referred for genetic counseling for her then current pregnancy because her existing 3-year-old son was diagnosed with a classic form of PMD. At 11 and 3/7 weeks gestation, chorionic villus sampling (CVS) was performed. Custom aCGH and fluorescence in situ hybridization (FISH) analyses were also performed on the DNA from family members. Fetal karyotyping revealed 46,XY. Results Analysis by aCGH revealed that the male fetus was not duplicated for the PLP1 gene, but confirmed a duplicated PLP1 gene in the 3-year-old son, and that the mother was a duplication carrier. These results were independently confirmed by FISH analysis. aCGH and FISH analyses on DNA and cells derived from cord blood confirmed PLP1 nonduplication in the newborn. Conclusion aCGH is a reliable alternative method for detection of PLP1 copy number for prenatal diagnosis of Pelizaeus-Merzbacher disease. Copyright © 2005 John Wiley & Sons, Ltd.