Multiplex ligation-dependent probe amplification for rapid detection of proteolipid protein 1 gene duplications and deletions in affected males and carrier females with Pelizaeus-Merzbacher disease

Clinical Chemistry
Ilka WarshawskyMarvin R Natowicz

Abstract

Pelizaeus-Merzbacher disease is a rare X-linked neurodegenerative disorder caused by sequence variations in the proteolipid protein 1 gene (PLP1). PLP1 gene duplications account for approximately 50%-75% of cases and point variations for approximately 15%-20% of cases; deletions and insertions occur infrequently. We used multiplex ligation-dependent probe amplification (MLPA) to detect PLP1 gene alterations, especially gene duplications and deletions. We performed MLPA on 102 samples from individuals with diverse PLP1 gene abnormalities and from controls, including 50 samples previously characterized for the PLP1 gene by quantitative PCR but which were anonymized for prior results and sex. All males with PLP1 gene duplications (n = 13), 1 male with a triplication, 2 males with whole gene deletions, and all controls (n = 72) were unambiguously assigned to their correct genotype. Of 4 female carriers tested by MLPA and quantitative PCR, 3 were duplication carriers by both methods, and 1 was a triplication carrier by MLPA and a duplication carrier by quantitative PCR. For 1 sample with a partial deletion, MLPA showed exon 3 deleted but PCR showed exons 3 and 4 deleted. Sequence analysis of 2 samples with reduced dosage for exons 3...Continue Reading

References

Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·H J DiehlW Stoffel
Apr 1, 1994·Nature Genetics·D Ellis, S Malcolm
Feb 13, 1995·American Journal of Medical Genetics·D O KleindorferM E Hodes
Sep 6, 2001·Pharmacogenomics·K Woodward, S Malcolm
Oct 29, 2002·Human Mutation·J A L ArmourG R Taylor
Feb 26, 2003·Annals of Neurology·Michael E ShyJohn Kamholz
Feb 28, 2003·American Journal of Medical Genetics. Part a·Karen WoodwardSue Malcolm
Dec 18, 2004·Methods in Cell Biology·Stefan J WhiteJohan T den Dunnen
Feb 4, 2005·Brain : a Journal of Neurology·Nicole I WolfKaren J Woodward
Feb 16, 2005·Human Mutation·Christian A HübnerAndreas Gal
Mar 10, 2005·American Journal of Human Genetics·Pawandeep DhamiDavid Vetrie
Apr 22, 2005·BMC Medical Genetics·Dorte DamgaardOle Faergeman
Apr 29, 2005·The Journal of Molecular Diagnostics : JMD·Linnea M BaudhuinStephen N Thibodeau

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Citations

May 20, 2008·Expert Reviews in Molecular Medicine·Karen J Woodward
Mar 14, 2013·Congenital Anomalies·Toshiyuki Yamamoto, Keiko Shimojima

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