title: First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency.
abstract: OBJECTIVE
  We report on the first prenatal molecular diagnosis of holocarboxylase synthetase (HLCS) deficiency in the fourth pregnancy of an at-risk family. This disorder is a rare autosomal recessive inborn error of metabolism, leading to a multiple carboxylase defect (MCD). HLCSD diagnosis was performed postmortem in the proband on DNA from autoptic biological material. Molecular analysis of the proband's entire HLCS gene by direct sequencing identified the R508W amino acid change, at the homozygous status.
  
  
  METHODS
  Fetal DNA was isolated from chorionic villus sampling at 11 weeks of gestation. Direct sequencing of exon 6 of the fetal HLCS gene was performed.
  
  
  RESULTS
  The R508W mutation was identified in the fetal DNA at the homozygous level. The genetic lesion was confirmed on abortive tissue.
  
  
  CONCLUSIONS
  Molecular diagnosis has several advantages over enzymatic activity assay of carboxylases in chorionic villi or amniocytes. It can be performed earlier, is faster, and the response time is shorter.
authors.affiliation: Metabolic and Muscular Unit, Department of Pediatrics, University of Florence, Meyer Children's Hospital, Florence, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pasquini
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Enrico
authors.initials: E
authors.lastname: Zammarchi
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: Donati
mesh_terms: D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D028922:Holocarboxylase Synthetase Deficiency / Q000175:diagnosis* / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011295:Prenatal Care; D011296:Prenatal Diagnosis
chemical_list: D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases