Abstract
A family with a history of Pelizaeus-Merzbacher disease (PMD) received prenatal diagnosis of PLP1 gene duplication in a fetus using a single nucleotide polymorphism (SNP) array. A 27-year-old pregnant woman was referred for genetic counseling due to her four-year-old son being diagnosed with a suspected classic type of PMD. Amniocentesis was performed at 18 and 3/7 weeks of gestation, and the SNP array was carried out on DNA from the mother, her affected son, and fetus, then further confirmed by multiplex ligation-dependent probe amplification (MLPA). Cytogenetic analysis of the fetus showed 46,XY. SNP array analysis revealed that the male fetus did not carry PLP1 gene duplication but the affected boy did, and the mother was a carrier for the duplication of the PLP1 gene. All SNP array results were further confirmed by MLPA. SNP array and MLPA analyses of peripheral blood verified the nonduplication of the PLP1 gene in the infant after birth. At present, the child (without PLP1 duplication) is developing normally. This study preliminarily suggests that SNP array is a sensitive and accurate technology for identifying PLP1 duplication and is feasible for reliable diagnosis, including for the prenatal diagnosis of PMD resulting from PLP1 duplication.
Highlights
Pelizaeus-Merzbacher disease (PMD; MIM 312080) is a rare X-linked recessive demyelinating central nervous system (CNS) disorder [1]
The brain magnetic resonance imaging (MRI) findings of the proband were consistent with PMD
multiplex ligation-dependent probe amplification (MLPA) analysis of cultured amniocytes revealed that the male fetus did not have PLP1 duplication (Figure 4C), confirming the original single nucleotide polymorphism (SNP) array analysis. These findings indicate that the proband could be diagnosed with PMD caused by the duplicated PLP1 gene, inherited from his unaffected carrier mother
Summary
Pelizaeus-Merzbacher disease (PMD; MIM 312080) is a rare X-linked recessive demyelinating central nervous system (CNS) disorder [1]. The gene that causes PMD is PLP1, which is located on chromosome Xq22.2. PLP1 consists of seven exons that encode two splicing isoforms (PLP1 and DM20). Affected male patients’ mothers are often carriers of PLP1 variations and are often asymptomatic, they are at a 50% risk of having male children with PMD. There is no definitive treatment for PMD. Accurate prenatal genetic diagnoses are necessary for high-risk couples
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