title: A Large Intragenic Deletion in the ACADM Gene Can Cause MCAD Deficiency but is not Detected on Routine Sequencing.
abstract: We report of a family who has three members affected by medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, one of whom sadly died in the neonatal period prior to diagnosis. Routine sequencing, available on a service basis in the UK, identified only a heterozygous mutation in ACADM gene (c.985A>G, p.Lys329Glu) in this family. Linkage analysis suggested a possible intragenic deletion which was confirmed by the use of array-based comparative genomic hybridization (aCGH). This second mutation was a large intragenic deletion encompassing at least exons 1-6 of the ACADM gene. Now that this deletion has been identified, several family members have come forward for carrier testing which was not possible previously. Larger deletions (20bp or more) have only previously been reported twice, but these may be a more frequent cause of MCAD deficiency than hitherto believed, due to fact that these are not anticipated and, therefore, the routine diagnostic techniques used will not identify them. This finding represents a useful learning point in the management of families with MCAD deficiency, and highlights that we should be routinely looking for larger deletions, when only one of the mutations can be identified on standard sequencing.
authors.affiliation: Yorkshire Regional Genetic Service, Chapel Allerton Hospital, Chapeltown Rd, Leeds, LS7 4SA, UK, cjs29@doctors.org.uk.
authors.forename: Claire
authors.initials: C
authors.lastname: Searle
authors.forename: Brage Storstein
authors.initials: BS
authors.lastname: Andresen
authors.forename: Ed
authors.initials: E
authors.lastname: Wraith
authors.forename: Jamie
authors.initials: J
authors.lastname: Higgs
authors.forename: Deborah
authors.initials: D
authors.lastname: Gray
authors.forename: Alison
authors.initials: A
authors.lastname: Mills
authors.forename: K Elizabeth
authors.initials: KE
authors.lastname: Allen
authors.forename: Emma
authors.initials: E
authors.lastname: Hobson
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