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Variable Expression of a Novel PLP1 Mutation in Members of a Family With Pelizaeus-Merzbacher Disease

Institute for Child Development and Pediatric Neurology Unit, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Miriam S. DiMaio, MSW

Department of Genetics, Yale University School of Medicine, New Haven, Connecticut

Fuki M. Hisama, MD

Division of Genetics, Children's Hospital Boston, Boston, Massachusetts

Grace M. Hobson, PhD

Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware

Angelique Davis-Williams, MS

Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware

James Y. Garbern, MD

Department of Neurology and Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan

Maurice J. Mahoney, MD, JD

Department of Genetics, Yale University School of Medicine, New Haven, Connecticut

Edwin H. Kolodny, MD

Division of Neurogenetics, Department of Neurology, New York University School of Medicine, New York

Gregory M. Pastores, MD

Division of Neurogenetics, Department of Neurology, New York University School of Medicine, New York, gregory.pastores{at}med.nyu.edu

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.

Key Words: Pelizaeus-Merzbacher disease • proteolipid protein • nystagmus • cerebral palsy • preimplantation genetic diagnosis

This version was published on May 1, 2009

Journal of Child Neurology, Vol. 24, No. 5, 618-624 (2009)
DOI: 10.1177/0883073808327833


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