title: Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1.
abstract: We describe two brothers who presented at birth with bone growth abnormalities, followed by development of increasingly severe intellectual and physical disability, growth restriction, epilepsy, and cerebellar and brain stem atrophy, but normal ocular phenotypes. Case 1 died at 19 years of age due to chronic respiratory illnesses without a unifying diagnosis. The brother remains alive but severely disabled at 19 years of age. Whole exome sequencing identified compound heterozygous stop mutations in the peroxisome biogenesis factor 7 gene in both individuals. Mutations in this gene cause rhizomelic chondrodysplasia punctata, type 1 (RCDP1). One mutation, p.Arg232 (∗) , has only been documented once before in a Japanese family, which is of interest given these two boys are of European descent. The other mutation, p.Leu292 (∗) , is found in approximately 50% of RCDP1 patients. These are the first cases of RCDP1 that describe the coinheritance of the p.Arg232 (∗) and p.Leu292 (∗) mutations and demonstrate the utility of WES in cases with unclear diagnoses.
authors.affiliation: Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand.
authors.forename: Jessie C
authors.initials: JC
authors.lastname: Jacobsen
authors.affiliation: Adult and Paediatric National Metabolic Service, Auckland City Hospital, Auckland 1142, New Zealand.
authors.forename: Emma
authors.initials: E
authors.lastname: Glamuzina
authors.affiliation: Genetic Health Service New Zealand, Auckland City Hospital, Auckland 1142, New Zealand.
authors.forename: Juliet
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand.
authors.forename: Brendan
authors.initials: B
authors.lastname: Swan
authors.affiliation: Department of Radiology, Auckland City Hospital, Auckland 1142, New Zealand.
authors.forename: Shona
authors.initials: S
authors.lastname: Handisides
authors.affiliation: Adult and Paediatric National Metabolic Service, Auckland City Hospital, Auckland 1142, New Zealand.
authors.forename: Callum
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Department of Biochemical Genetics, SA Pathology, North Adelaide, SA 5006, Australia ; Department of Diagnostic Genomics, PathWest, Nedlands, WA 6009, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fietz
authors.affiliation: Department of Genome Analysis, Academic Medical Centre, 1105 Amsterdam, Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: van Dijk
authors.affiliation: Department of Genome Analysis, Academic Medical Centre, 1105 Amsterdam, Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Appelhof
authors.affiliation: Department of Neurology, Auckland City Hospital, Auckland 1142, New Zealand.
authors.forename: Rosamund
authors.initials: R
authors.lastname: Hill
authors.affiliation: Developmental Paediatric Service, Starship Children's Health, Auckland 1142, New Zealand.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Marks
authors.affiliation: Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland 1142, New Zealand.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Love
authors.affiliation: Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.affiliation: Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Snell
authors.affiliation: Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lehnert