title: Somatic mosaicism for a novelPDHA1mutation in a male with severe pyruvate dehydrogenase complex deficiency.
abstract: Pyruvate dehydrogenase complex (PDC) deficiencies are mostly due to mutations in the X-linkedPDHA1gene. Males with hemizygousPDHA1mutations are clinically more severely affected, while those with mosaicPDHA1mutations may manifest milder phenotypes. We report a patient harboring a novel, mosaic missensePDHA1mutation, c.523G > A (p.A175T), with a severe clinical presentation of congenital microcephaly, significant brain abnormalities, persistent seizures, profound developmental delay, and failure to thrive. We review published cases ofPDHA1mosaicism.
authors.affiliation: Center for Human Genetics Laboratory University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Deeb
authors.affiliation: Center for Inherited Disorders of Energy Metabolism (CIDEM), University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Jirair K
authors.initials: JK
authors.lastname: Bedoyan
authors.affiliation: Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Wang
authors.affiliation: Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, USA.
authors.forename: Leighann
authors.initials: L
authors.lastname: Sremba
authors.affiliation: Center for Human Genetics Laboratory University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Molly C
authors.initials: MC
authors.lastname: Schroeder
authors.affiliation: Center for Inherited Disorders of Energy Metabolism (CIDEM), University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Grahame
authors.affiliation: Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Boyer
authors.affiliation: Center for Inherited Disorders of Energy Metabolism (CIDEM), University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: McCandless
authors.affiliation: Center for Inherited Disorders of Energy Metabolism (CIDEM), University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kerr
authors.affiliation: Center for Human Genetics Laboratory University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhang
keywords: Mosaicism; Mutation analysis; PDHA1 gene; PDHc Deficiency