title: The first prenatal diagnosis for veno-occlusive disease and immunodeficiency syndrome, an autosomal recessive condition associated with mutations in SP110.
abstract: OBJECTIVE
  We present the first prenatal diagnosis of familial hepatic veno-occlusive disease with immunodeficiency (VODI). Homozygous mutations in the gene SP110 are the genetic basis of VODI. The proband in this report presented at three months of age with hepatomegaly hepatic failure and was found to have hypogammaglobulinemia. He died one month after hepatic transplant at eight months of age due to hemophagocytic syndrome. DNA testing detected a homozygous truncating mutation in exon 5; SP110 c.642delC. Prenatal testing was offered to this family in a subsequent pregnancy.
  
  
  METHODS
  Chorion villus was sampled at 12 weeks' gestation. DNA was extracted using standard techniques, and sequencing of SP110 exon 5 was performed using flanking primers. Maternal contamination was excluded by examining STR markers in CVS and maternal DNA.
  
  
  RESULTS
  A heterozygous SP110 c.642delC mutation was detected in exon 5. This mutation was present in heterozygous form in both parents.
  
  
  CONCLUSIONS
  The prenatal test result is predictive of a child with a normal immune and hepatic phenotype. This report presents the first prenatal molecular diagnosis for VODI and shows the importance of molecular genetic research in not only defining the aetiology of syndromes but also in assisting reproductive choices through the collaboration of genetic and feto-maternal services.
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, Australia. simon.cliffe@sesiahs.health.nsw.gov.au
authors.forename: Simon T
authors.initials: ST
authors.lastname: Cliffe
authors.forename: Melanie
authors.initials: M
authors.lastname: Wong
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Taylor
authors.forename: Ezia
authors.initials: E
authors.lastname: Ruga
authors.forename: Bridget
authors.initials: B
authors.lastname: Wilcken
authors.forename: Robert
authors.initials: R
authors.lastname: Lindeman
authors.forename: Michael F
authors.initials: MF
authors.lastname: Buckley
authors.forename: Tony
authors.initials: T
authors.lastname: Roscioli
mesh_terms: D015193:Chorionic Villi Sampling; D018389:Codon, Nonsense; D005260:Female; D005808:Genes, Recessive; D006504:Hepatic Veno-Occlusive Disease / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy
chemical_list: D018389:Codon, Nonsense; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C412425:Sp110 protein, human