Deletions of PLP1 locus (which are rare) cause a milder form of Pelizaeus–Merzbacher disease than is observed with the typical duplication mutations, which demonstrates the critical importance of gene dosage at this locus for normal CNS function. Diagnosis
The diagnosis of Pelizaeus–Merzbacher disease is often first suggested after identification by magnetic resonance imaging of abnormal white matter (high T2 signal intensity, i.e. T2 lengthening) throughout the brain, which is typically evident by about 1 year of age, but more subtle abnormalities should be evident during infancy. Unless a family history consistent with sex-linked inheritance exists, the condition is often misdiagnosed as cerebral palsy. Once a PLP1 mutation is identified, prenatal diagnosis or preimplantation genetic diagnostic testing is possible. Classification
The disease is one in a group of genetic disorders collectively known as leukodystrophies that affect the growth of the myelin sheath, the fatty covering—which acts as an insulator—on nerve fibers in the central nervous system. The several forms of Pelizaeus–Merzbacher disease include classic, congenital, transitional, and adult variants.Milder mutations of the PLP1 gene that mainly cause leg weakness and spasticity, with little or no cerebral involvement, are classified as spastic paraplegia 2 (SPG2). Treatment
No cure for Pelizaeus–Merzbacher disease has been developed. Outcomes are variable: people with the most severe form of the disease do not usually survive to adolescence, although with milder forms, survival into adulthood is possible. Research
In December 2008, StemCells, Inc received clearance in the United States to conduct a phase I clinical trials of human neural stem cell transplantation.
The trial did not show meaningful efficacy and the company has since gone bankrupt.In 2019 Paul Tesar, a professor at Case Western Reserve University, used CRISPR and antisense therapy in a mouse model of Pelizaeus–Merzbacher with success. In 2022 Case Western Reserve University entered a exclusive licensing agreement with Ionis Pharmaceuticals to develop a human treatment for the disorder. See also
The Myelin Project
The Stennis Foundation

References
Further reading
Uhlenberg, Birgit; Schuelke, Markus; Rüschendorf, Franz; Ruf, Nico; Kaindl, Angela M.; Henneke, Marco; Thiele, Holger; Stoltenburg-Didinger, Gisela; Aksu, Fuat; Topaloğlu, Haluk; Nürnberg, Peter; Hübner, Christoph; Weschke, Bernhard; Gärtner, Jutta (August 2004). "Mutations in the Gene Encoding Gap Junction Protein α12 (Connexin 46.6) Cause Pelizaeus-Merzbacher–Like Disease". The American Journal of Human Genetics. 75 (2): 251–260. doi:10.1086/422763. PMC 1216059. PMID 15192806. External links
Pelizaeus-Merzbacher Disease - PMD Foundation
Pelizaeus-Merzbacher Disease. NINDS/National Health Institutes. pmd at NIH/UW GeneTests