title: Variable expression of a novel PLP1 mutation in members of a family with Pelizaeus-Merzbacher disease.
abstract: Pelizaeus-Merzbacher disease is a rare X-linked disorder caused by mutations of the proteolipid protein 1 gene that encodes a structural component of myelin. It is characterized by progressive psychomotor delay, nystagmus, spastic quadriplegia, and cerebellar ataxia. Variable clinical expression was seen in 5 members of a family bearing a novel missense mutation in proteolipid protein 1, c.619T>C. Symptomatic patients included a 6-year-old girl, her younger brother, and their maternal uncle, a 29-year-old college graduate initially diagnosed with cerebral palsy; their brain magnetic resonance imaging studies showed diffuse dysmyelination. The mother had a history of delayed walking, achieved independently by age 3; she and the maternal grandmother were asymptomatic on presentation. Review of clinical information and family history led to consideration of Pelizaeus-Merzbacher disease. Subsequent identification of the causal mutation enabled preimplantation genetic diagnosis and the birth of an unaffected child.
authors.affiliation: Institute for Child Development and Pediatric Neurology Unit, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Fattal-Valevski
authors.forename: Miriam S
authors.initials: MS
authors.lastname: DiMaio
authors.forename: Fuki M
authors.initials: FM
authors.lastname: Hisama
authors.forename: Grace M
authors.initials: GM
authors.lastname: Hobson
authors.forename: Angelique
authors.initials: A
authors.lastname: Davis-Williams
authors.forename: James Y
authors.initials: JY
authors.lastname: Garbern
authors.forename: Maurice J
authors.initials: MJ
authors.lastname: Mahoney
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D002547:Cerebral Palsy / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D009186:Myelin Sheath / Q000473:pathology; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D019836:Preimplantation Diagnosis
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human