title: Paternal isodisomy of chromosome 2 as a cause of long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.
abstract: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is an autosomal recessive disorder affecting mitochondrial fatty acid oxidation due to mutations in the HADHA gene. We report on a 22-month-old child who was identified on expanded newborn screening with an abnormal acylcarnitine pattern and increased C14OH. Molecular analysis showed that the child was homozygous for the common mutation, c.1526G > C (p.Glu510Gln) in the HADHA gene. Carrier testing on the parental samples revealed that the father was heterozygous for the mutation whereas the mother did not carry the mutation. Short tandem repeat testing with markers covering both short and long arms of chromosome 2 showed that the child has paternal uniparental isodisomy. We highlight the importance of parental testing in cases of homozygosity in autosomal recessive disorders and its impact on genetic counseling of the family.
authors.affiliation: Division of Molecular Genetics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada. berivan.baskin@sickkids.ca
authors.forename: Berivan
authors.initials: B
authors.lastname: Baskin
authors.forename: Michael
authors.initials: M
authors.lastname: Geraghty
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ray
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D001483:Base Sequence; D020090:Chromosome Segregation / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011247:Pregnancy; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase