Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report

Abstract

Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy with clinical symptoms and imaging manifestations similar to those of Pelizaeus-Merzbacher disease (PMD), an X-linked recessive hypomyelinating leukodystrophy. Typical manifestations of PMLD are nystagmus, dysmyotonia, ataxia, progressive motor dysfunction, and diffuse leukodystrophy on magnetic resonance imaging (MRI). This report identified novel mutations in NCP1 causing PMLD. A 7-month-old male patient was referred to our hospital because he could not lift his head until that time. He had symptoms including congenital nystagmus, hypotonia, and developmental delay. According to the MRI scan, there were signs of leukodystrophy. According to the clinical manifestations and the results of whole-exome sequencing (compound heterozygote mutations in NPC1 (p. G911S, c2731G>A and p. D128H, c382G>C)), the diagnosis of PMLD was considered, and his parents were determined to be carriers of mutant genes. He began rehabilitation training at the age of 1 year old. After 5 years of training, he was still experiencing global developmental delay, equivalent to the developmental level of a nine-month-old child. PMLD is a disease that seriously affects the quality of life of children and can result from mutations in different genes. In this report, we expand the gene spectrum of PMLD and suggest early genetic counselling for suspected patients and their patients.

Mechanisms of Diseases Associated with Mutation in GJC2/Connexin 47

“…The NORD Rare disease database (accessed on 11 March 2023) separates PMLD (caused by GJC2 mutations) from their list of other diseases that need to be distinguished from PMD. Nonetheless, the term PMLD has also been used recently to describe both an unusual case associated with mutations in NPC1, the gene associated with Niemann Pick disease types C1 and D [ 127 ] and a RARS mutation associated hypomyelinating phenotype [ 128 ].…”