First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency.
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.
Malvagia
Sabrina
S
Metabolic and Muscular Unit, Department of Pediatrics, University of Florence, Meyer Children's Hospital, Florence, Italy.
Morrone
Amelia
A
Pasquini
Elisabetta
E
Funghini
Silvia
S
la Marca
Giancarlo
G
Zammarchi
Enrico
E
Donati
Maria Alice
MA
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
D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases