Preimplantation genetic diagnosis for Niemann-Pick disease type B.

Background: Acid sphingomyelinase (ASM) deficient Niemann-Pick disease (NPD) is an autosomal recessive disorder caused by mutations in the ASM gene (SMPD1). More than 70 different mutations have been reported in this gene. NPD type B is the most common type in Saudi Arabia with a frequency of 1:40 000 to 1:100 000. The phenotype of Saudi Type B patients is more severe than patients reported from the West. Two mutations specific to Saudi patients have been inherited in the SMPD1 gene. Given the difficult management of the disease, we opted for a preventive approach to the suffering families by screening the whole SMPD1 gene for mutations followed by Preimplantation Genetic Diagnosis (PGD).

Methods: The family suffering from NPD-B underwent mutation screening for the entire SMPD1 gene followed by PGD using nested PCR and sequencing.

Results: A novel mutation in a family suffering from the same severe NPD-B phenotype is described in this report (W533R). After PGD, a singleton pregnancy ensued after transfer of one heterozygous and one normal embryo. Postnatal DNA testing of the newborn showed a normal homozygous genotype.

Conclusions: This report reveals a new SMPD1 mutation responsible for similar Saudi severe phenotype, and the prevention of this disorder by PGD.