PLP1 gene duplication as a cause of the classic form of Pelizaeus-Merzbacher disease - case report

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelination disorder of the central nervous system (CNS). PMD is caused by mutations in the PLP1 gene located at Xq22 and encoding the major myelin component in CNS, proteolipid protein 1 (PLP1). The disease is clinically heterogeneous. Phenotypes are generally categorized into classic and connatal forms. Connatal PMD has more rapid progression with early death, while patients with classic PMD generally survive to adulthood. Both forms of the disease are caused by point mutations as well as rearrangements - multiplication (mainly duplication) and deletion of the PLP1 gene. We present a case of a male patient affected by the classic form of PMD with benign course, except severe dysarthria with the characteristic laryngeal stridor, which is more typical for connatal form of the disease. The diagnosis has been confirmed at the molecular level. The patient has duplication of all 7 exons of the PLP1 gene. This duplication was inherited from the patient's mother, who is an unaffected carrier of the mutation. The patient's family pedigree analysis revealed the interfamilial variability of the phenotype among affected male relatives.