title: WDR45 mutations in Rett (-like) syndrome and developmental delay: Case report and an appraisal of the literature.
abstract: Mutations in the WDR45 gene have been identified as causative for the only X-linked type of neurodegeneration with brain iron accumulation (NBIA), clinically characterized by global developmental delay in childhood, followed by a secondary neurological decline with parkinsonism and/or dementia in adolescence or early adulthood. Recent reports suggest that WDR45 mutations are associated with a broader phenotypic spectrum. We identified a novel splice site mutation (c.440-2 A > G) in a 5-year-old Argentinian patient with Rett-like syndrome, exhibiting developmental delay, microcephaly, seizures and stereotypic hand movements, and discuss this finding, together with a review of the literature. Additional patients with a clinical diagnosis of Rett (-like) syndrome were also found to carry WDR45 mutations before (or without) clinical decline or signs of iron accumulation by magnetic resonance imaging (MRI). This information indicates that WDR45 mutations should be added to the growing list of genetic alterations linked to Rett-like syndrome. Further, clinical symptoms associated with WDR45 mutations ranged from early-onset epileptic encephalopathy in a male patient with a deletion of WDR45 to only mild cognitive delay in a female patient, suggesting that analysis of this gene should be considered more often in patients with developmental delay, regardless of severity. The increasing use of next generation sequencing technologies as well as longitudinal follow-up of patients with an early diagnosis will help to gain additional insight into the phenotypic spectrum associated with WDR45 mutations.
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Germany; Center for Rare Diseases Ruhr (CeSER), Bochum, Germany. Electronic address: sabine.hoffjan@rub.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Germany; Center for Rare Diseases Ruhr (CeSER), Bochum, Germany.
authors.forename: Aysegül
authors.initials: A
authors.lastname: Ibisler
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Tschentscher
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Germany; Center for Rare Diseases Ruhr (CeSER), Bochum, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
authors.affiliation: Sanatorio Allende and Fundación Allende, Córdoba, Argentina.
authors.forename: Carla
authors.initials: C
authors.lastname: Bidinost
authors.affiliation: Sanatorio Allende and Fundación Allende, Córdoba, Argentina.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Rosa
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics; D015518:Rett Syndrome; D012689:Sequence Homology, Nucleic Acid
chemical_list: D002352:Carrier Proteins; D022821:RNA Splice Sites; C578284:WDR45 protein, human
keywords: BPAN; Intellectual disability; NBIA; Rett syndrome; WDR45