title: Preimplantation genetic diagnosis for Niemann-Pick disease type B.
abstract: 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.
authors.affiliation: King Faisal Specialist Hospital and Research Center, PO Box 3354, MBC #10, Riyadh 11211, Saudi Arabia. hellani@kfshrc.edu.sa
authors.forename: Ali
authors.initials: A
authors.lastname: Hellani
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Odaib
authors.forename: Aida
authors.initials: A
authors.lastname: Al Aqueel
authors.forename: Kamal
authors.initials: K
authors.lastname: Jaroudi
authors.forename: Pinar
authors.initials: P
authors.lastname: Ozand
authors.forename: Serdar
authors.initials: S
authors.lastname: Coskun
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA; D020554:Sperm Injections, Intracytoplasmic; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: D013108:Sphingomyelin Phosphodiesterase