Variable expression of a novel PLP1 mutation in members of a family with Pelizaeus-Merzbacher disease.
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.
Fattal-Valevski
Aviva
A
Institute for Child Development and Pediatric Neurology Unit, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
DiMaio
Miriam S
MS
Hisama
Fuki M
FM
Hobson
Grace M
GM
Davis-Williams
Angelique
A
Garbern
James Y
JY
Mahoney
Maurice J
MJ
Kolodny
Edwin H
EH
Pastores
Gregory M
GM
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
D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human