Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia
Pelizaeus–Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)—a rare disorder that especially concerns males. Its estimated prevalence is 1.45–1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or...
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MDPI AG
2022-07-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1709 |
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| author | Guy Khalaf Claudia Mattern Mélina Begou Odile Boespflug-Tanguy Charbel Massaad Liliane Massaad-Massade |
| author_facet | Guy Khalaf Claudia Mattern Mélina Begou Odile Boespflug-Tanguy Charbel Massaad Liliane Massaad-Massade |
| author_sort | Guy Khalaf |
| collection | DOAJ |
| description | Pelizaeus–Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)—a rare disorder that especially concerns males. Its estimated prevalence is 1.45–1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or absence of myelin sheaths in the white matter areas of the CNS. The Proteolipid Protein 1 (<i>PLP1</i>) gene encodes a transmembrane proteolipid protein. PLP1 is the major protein of myelin, and it plays a key role in the compaction, stabilization, and maintenance of myelin sheaths. Its function is predominant in oligodendrocyte development and axonal survival. Mutations in the <i>PLP1</i> gene cause the development of a wide continuum spectrum of leukopathies from the most severe form of PMD for whom patients exhibit severe CNS hypomyelination to the relatively mild late-onset type 2 spastic paraplegia, leading to the concept of PLP1-related disorders. The genetic diversity and the biochemical complexity, along with other aspects of PMD, are discussed to reveal the obstacles that hinder the development of treatments. This review aims to provide a clinical and mechanistic overview of this spectrum of rare diseases. |
| first_indexed | 2024-03-09T10:22:11Z |
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| last_indexed | 2024-03-09T10:22:11Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-5e20e7ca452f460d97555da82facb8f12023-12-01T21:56:21ZengMDPI AGBiomedicines2227-90592022-07-01107170910.3390/biomedicines10071709Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic ParaplegiaGuy Khalaf0Claudia Mattern1Mélina Begou2Odile Boespflug-Tanguy3Charbel Massaad4Liliane Massaad-Massade5U1195 Diseases and Hormones of the Nervous System, INSERM and Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, FranceM&P Pharma, Schynweg 7, 6376 Emmetten, SwitzerlandNeuro-Dol, CNRS, Inserm, Université Clermont Auvergne, 63000 Clermont-Ferrand, FranceUMR 1141, INSERM, NeuroDiderot Université Paris Cité and APH-P, Neuropédiatrie, French Reference Center for Leukodystrophies, LEUKOFRANCE, Hôpital Robert Debré, 75019 Paris, FranceUMRS 1124, INSERM, Université Paris Cité, 75006 Paris, FranceU1195 Diseases and Hormones of the Nervous System, INSERM and Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, FrancePelizaeus–Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)—a rare disorder that especially concerns males. Its estimated prevalence is 1.45–1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or absence of myelin sheaths in the white matter areas of the CNS. The Proteolipid Protein 1 (<i>PLP1</i>) gene encodes a transmembrane proteolipid protein. PLP1 is the major protein of myelin, and it plays a key role in the compaction, stabilization, and maintenance of myelin sheaths. Its function is predominant in oligodendrocyte development and axonal survival. Mutations in the <i>PLP1</i> gene cause the development of a wide continuum spectrum of leukopathies from the most severe form of PMD for whom patients exhibit severe CNS hypomyelination to the relatively mild late-onset type 2 spastic paraplegia, leading to the concept of PLP1-related disorders. The genetic diversity and the biochemical complexity, along with other aspects of PMD, are discussed to reveal the obstacles that hinder the development of treatments. This review aims to provide a clinical and mechanistic overview of this spectrum of rare diseases.https://www.mdpi.com/2227-9059/10/7/1709Pelizaeus-Merzbacher disease (PMD)spastic paraplegia (SPG2)diagnosisproteolipid protein 1 variantsanimal modelstreatments |
| spellingShingle | Guy Khalaf Claudia Mattern Mélina Begou Odile Boespflug-Tanguy Charbel Massaad Liliane Massaad-Massade Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia Biomedicines Pelizaeus-Merzbacher disease (PMD) spastic paraplegia (SPG2) diagnosis proteolipid protein 1 variants animal models treatments |
| title | Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia |
| title_full | Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia |
| title_fullStr | Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia |
| title_full_unstemmed | Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia |
| title_short | Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia |
| title_sort | mutation of proteolipid protein 1 gene from severe hypomyelinating leukodystrophy to inherited spastic paraplegia |
| topic | Pelizaeus-Merzbacher disease (PMD) spastic paraplegia (SPG2) diagnosis proteolipid protein 1 variants animal models treatments |
| url | https://www.mdpi.com/2227-9059/10/7/1709 |
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