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Seventeen novel PLP1 mutations in patients with Pelizaeus‐Merzbacher disease
Author(s) -
Hübner Christian A.,
Orth Ulrike,
Senning Arne,
Steglich Cordula,
Kohlschütter Alfried,
Korinthenberg Rudolf,
Gal Andreas
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9314
Subject(s) - missense mutation , biology , genetics , exon , proteolipid protein 1 , gene duplication , gene , phenotype , mutation , leukodystrophy , point mutation , disease , pathology , myelin , medicine , central nervous system , myelin basic protein , neuroscience
Pelizaeus‐Merzbacher disease (PMD) is a rare X‐chromosomal neurodegenerative disorder that affects primarily the white matter of the central nervous system and is caused by mutations of the PLP1 (proteolipid protein 1) gene. We performed mutation analysis of 133 male patients with suspected PMD. Following SSCP analysis of all coding exons of PLP1 , we found most likely pathogenic mutations (single base substitutions and small rearrangements) including 17 novel sequence variants in 21 (15.8%) patients. Most patients with missense mutations had a severe phenotype. Twelve patients (9.0%) carried a duplication of the entire gene, as demonstrated by quantitative real‐time PCR, and presented with a variable clinical phenotype including mild, classical, and severe courses of disease. Two patients had large deletions, spanning approximately 115 kb, that included the PLP1 gene. In total, we identified pathogenic mutations involving PLP1 in 35 (26.3%) of the 133 patients analyzed. © 2005 Wiley‐Liss, Inc.