Genetic diagnosis of PLP gene duplications/deletions in patients with Pelizaeus-Merzbacher disease

• Published in: Clinical genetics Vol. 68; no. 5; pp. 466 - 467
• Main Authors: Gao, Q, Thurston, VC, Vance, GH, Dlouhy, SR, Hodes, ME
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Blackwell Publishing Ltd/Inc 01.11.2005; Blackwell
• Subjects: Biological and medical sciences; Chromosome aberrations; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis - methods; Gene Deletion; Gene Dosage; Gene Duplication; General aspects. Genetic counseling; Genetic Testing - methods; Humans; In Situ Hybridization, Fluorescence; Medical genetics; Medical sciences; Neurology; Pelizaeus-Merzbacher Disease - diagnosis; Pelizaeus-Merzbacher Disease - genetics; PMD; Polymerase Chain Reaction; Real-time PCR; Human; Nervous system diseases; Pelizaeus-Merzbacher disease; PMD; Patient; Real time; Cerebral disorder; Genetic disease; Polymerase chain reaction; Real-time PCR; Central nervous system disease; Deletion; Genetics; Degenerative disease; Gene duplication; Diagnosis; Molecular biology
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2005.00522.x

PMD is an X‐linked recessive disorder due to a proteolipid protein (PLP) deficiency. Duplications of PLP gene were shown to be the principle cause of the disorder, accounting for an estimated 50‐70% of cases. To define a simple and reliable method for genetic diagnosis of PMD, a group of 42 patients with clinical manifestation of PMD was analyzed by means of real‐time quantitative PCR. Parallel fluorescence in situ hybridization (FISH) analysis was performed on the same group of patients. Real‐time PCR found seventeen samples had increased gene dosage, whereas FISH detected sixteen duplicated samples. Both methods identified a sample with PLP gene deletion. Our results indicate that real‐time PCR is a sensitive and reliable method for the detection of gene duplications/deletions. We further discussed the advantages and limitations of each method in clinical diagnosis of PMD.