PELIZAEUS-MERZBACHER DISEASE (PMD)
PLP1 Sequencing
DNA ANALYSIS
Also see: Pelizaeus-Merzbacher Disease (PMD) - FISH Analysis

Pelizaeus-Merzbacher disease (PMD) is a rare X-chromosomal neurodegenerative disorder that affects primarily the white matter of the central nervous system. The hypomyelinating X-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD) [OMIM #312080] is characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity. The disease is caused by mutations in the PLP1 gene, which encodes proteolipid protein 1. PLP1 is the major component of myelin in the central nervous system and is also expressed in myelin of the peripheral nervous system 1. The gene encodes two proteins expressed abundantly in oligodendrocytes, the proteolipid protein (PLP) and its differently spliced isoform. PLP1 is thought to play a major role in myelin sheath formation by promoting sheath compaction, and its dosage seems to be tightly regulated. Duplication of PLP1 is the most frequent mutation found in approximately 50%-75% of PMD patients, and rare deletions have been reported in <2%. Point mutations in PLP1 are present in approximately 15%-25% of patients. DNA sequencing analysis of the PLP1 gene is available at the Baylor Medical Genetics Laboratories in patients who have tested negative for PLP1 gene duplication and deletion mutations.

Reasons for Referral:

Confirmation of clinical diagnosis of PMD in patients who are negative for PLP1 gene duplication or deletion.
Female carrier testing in PMD families in which a familial PLP1 mutation has been identified by sequencing
Prenatal testing in PMD families in which a familial PLP1 mutation has been identified by sequencing

Testing Methodology:

Sequencing Analysis: PCR amplification of seven exons contained in the PLP1 gene coding region is performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83904x7, 83912, 83909x14, 83898x10, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Cailloux F, et al. (2000) Eur. J. Hum. Genet. 8: 837-845.

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6127
Known Familial Mutation: 6128
Prenatal (Known Familial Mutation Only): 6133