Dört Aileden Pelizaeus-Merzbacher Sendromlu Altı Hastanın Klinik ve Moleküler Sitogenetik Analizleri

Amaç: Pelizaeus-Merzbacher Hastalığı, Xq22 kromozomu üzerindeki proteolipid protein (PLP) genindeki bir mutasyonun neden olduğu X’e bağlı resesif nadir görülen bir lökodistrofidir. PMD, nistagmus, spastik kuadripleji, ataksi ve gelişimsel gecikme ile karakterize erken başlangıçlı bir nörolojik bozukluktur. Genetik analiz, Pelizaeus-Merzbacher Hastalığında PLP genlerinin kodlama bölgesinde Xq22 mikroduplikasyonlarını (%60-70), nokta mutasyonlarını (%10-25) ve delesyonları (%5-10) tanımlamıştır. Bu çalışma, dört Türk ailede PLP1 delesyonu ve duplikasyonu olan altı hastayı değerlendirdi. Gereç ve Yöntemler: PLP1’in duplikasyonu ve delesyonunu saptamak için kromozomal mikroarray analizi ve multipleks ligasyona bağlı prob amplifikasyon deneyleri yapıldı. Bulgular: Bu dört ailede, iki erkek kardeşte PLP1 geninde hemizigot delesyonu, taşıyıcı annelerinde PLP1 geninde delesyon ve akraba olmayan diğer iki erkek ve bir kızda PLP1 duplikasyonu vardı. Ayrıca, PLP1 geninde hemizigot delesyona sahip olduğu tespit edilen iki erkek kardeş hastanın nadir vakasını belirledik. Taşıyıcı annelerinde açıklanamayan bunama vardı. Sonuç: Bu çalışmada, dört farklı aileden altı bireyin genetik etiyolojisi aydınlatılmaya çalışılırken, bu ailelerdeki PLP1 mutasyonunun genotip-fenotip korelasyonları belirlendi.

Anahtar Kelimeler:

Pelizaeus-Merzbacher Hastalığı, PLP1 Geni, Dismiyelinizan Hastalıklar

The Clinical and Molecular Cytogenetic Analyses of Six Patients with Pelizaeus-Merzbacher Disease From Four Families

Objective: Pelizaeus-Merzbacher Disease is a rare X-linked recessive leukodystrophy caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. PMD is an early-onset neurological disorder characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. Genetic analysis has identified Xq22 microduplications (60-70%), point mutations (10–25%), and deletions (5-10%) within the coding region of the PLP genes in Pelizaeus-Merzbacher Disease. This study evaluated six patients with PLP1 deletion and duplication in four Turkish families. Material and Methods: To detect the duplication and deletion of PLP1, chromosomal microarray analysis, and multiplex ligation-related probe amplification assays were performed. Results: In these four families, two brothers had a hemizygous deletion in the PLP1 gene, their carrier mother had a deletion in the PLP1 gene, and another two unrelated boys and one girl had duplication of the PLP1. Also, we identified the rare case of two brother patients who were found to have a hemizygous deletion in the PLP1 gene. Their carrier mother had unexplained dementia. Conclusion: Genotype-phenotype correlations of the PLP1 mutation in these families were identified in this study while trying to elucidate the genetic etiology of six individuals from four different families.

Keywords:

Pelizaeus-Merzbacher Disease, PLP1 Gene, Dysmyelinating Disorders,

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