Variable expression of a novel PLP1 mutation in members of a family with Pelizaeus-Merzbacher disease

TitleVariable expression of a novel PLP1 mutation in members of a family with Pelizaeus-Merzbacher disease
Publication TypeJournal Article
Year of Publication2009
AuthorsFattal-Valevski, A., DiMaio M. S., Hisama F. M., Hobson G. M., Davis-Williams A., Garbern J. Y., Mahoney M. J., Kolodny E. H., & Pastores G. M.
JournalJournal of child neurology
Date Published2009 May
KeywordsAdult; Brain; Cerebral Palsy; Child; Child, Preschool; Diagnosis, Differential; DNA Mutational Analysis; Family; Female; Humans; Male; Middle Aged; Mutation, Missense; Myelin Proteolipid Protein; Myelin Sheath; Pedigree; Pelizaeus-Merzbacher Disease; Point Mutation; Preimplantation Diagnosis

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.

Alternate JournalJ. Child Neurol
Refereed DesignationRefereed