Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications

Clinical Genetics
Stefano RegisMirella Filocamo

Abstract

Pelizaeus-Merzbacher disease (PMD) is an X-linked myelination disorder most frequently caused by duplication of a genomic segment of variable length containing the PLP1 gene. We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical and neuroradiological features, two of the five patients appeared to be the most severely affected. In order to establish a possible genotype-phenotype correlation, the extent of the duplication was determined in each patient and in the respective mother by quantifying the copy number of genomic markers surrounding the PLP1 gene by a real-time PCR-based approach. Duplications, ranging in size from 167-195 to 580-700 kb, were in the same genomic interval of the majority of the reported duplications. The extent of the duplicated genomic segments does not correlate with the clinical severity. Interestingly enough, each duplication had one of the two breakpoints in or near to low copy repeats (LCRs), supporting recent evidence concerning a possible role of LCRs in the generation of the duplications in PMD.

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Citations

Feb 24, 2009·Orphanet Journal of Rare Diseases·Damien SanlavilleCatherine Turleau
Jul 19, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kristi ClarkGrace M Hobson
May 6, 2014·Imaging in Medicine·Wint Yan AungTammie Ls Benzinger
Nov 27, 2014·American Journal of Medical Genetics. Part a·Mathilde NizonValérie Malan
Jan 20, 2009·Journal of Child Neurology·Aviva Fattal-ValevskiGregory M Pastores
Apr 27, 2018·American Journal of Medical Genetics. Part a·Giovanni NeriRoger E Stevenson
Mar 29, 2013·The Journal of Genetic Psychology·Stefania AlbanoSimonetta D'Amico
Jan 18, 2020·Molecular Genetics & Genomic Medicine·Swati R ChanchaniPhilip F Giampietro

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