Novel mutation in PLP1 gene in an individual with Pelizaeus-Merzbacher disease (PMD) using whole exome sequencing

Background: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked genetic disorder affecting the central nervous system. This disease is associated with abnormalities of the white matter of the brain and spinal cord. It is a subgroup of leukodystrophies caused by abnormalities in one or more components (mainly fat or protein) that contribute to the formation of the white matter (myelin sheath) of the brain. Point mutations account for the remaining 20% of cases and are associated with highly variable phenotypes. These cases can range from mild to severe congenital clinical forms. Case Presentation: A family with one affected person studied in Baghdad, Iraq. The causative gene identified by exome sequencing. Exome sequencing results showed that a c.772A > C; p. Met258Leu mutation exists in the affected son of this family. To confirm the presence of the pathogenic PLP1 mutation, we performed direct Sanger sequencing on the patient and his mother. He was a hemizygous for this mutation while his mother was heterozygous. Conclusion: Our findings broaden the range of pathogenic mutations in PLP1 associated with the PMD disease, which is essential for the disease's genetic diagnosis and screening. This finding supports earlier studies indicating a connection between mutations in the PLP1 gene and PMD. Our research can assist in offering proper genetic counseling to the families impacted and helps enhance our understanding of how the PLP1 gene functions in PMD.