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Background: Minichromosome maintenance complex component 3 associated protein ( MCM3AP ) is a gene in which mutations can result in autosomal recessive peripheral neuropathy with or without impaired intellectual development. The MCM3AP genotype-phenotype correlation and prognosis remain unclear. The aim of this study was to explore the genotype-phenotype correlations pertaining to MCM3AP ., Methods: Whole-exome sequencing (WES) combined with copy number variation sequencing (CNV-seq) were performed on the genomic DNA isolated from a Chinese family, and Sanger sequencing, quantitative PCR and cDNA analyses were performed to examine the mutations. The retrospective study was conducted on 28 individuals with biallelic MCM3AP mutation-related diseases, including features such as mutations, motor development impairment, intellectual disability, weakness/atrophy, and cerebral magnetic resonance imaging abnormalities., Results: Sequencing identified novel compound heterozygous mutations in MCM3AP , namely, a paternal variant c.1_5426del (loss of exons 1-25) and a maternal splicing variant c.1858 + 3A>G. Functional studies revealed that the variant c.1858 + 3A>G resulted in the heterozygous deletion of exon 5, thereby affecting splicing functionality. Furthermore, the compound heterozygous mutation may affect the functionality of the protein domain. Retrospective analysis revealed different genotype-phenotype correlations for the pathogenic variants in biallelic MCM3AP : all individuals (100%) with mutations outside the Sac3 domain exhibited early-onset symptoms, motor developmental delays, and cognitive abnormalities, conversely, the proportions of individuals carrying mutations within the domain were 26.7% (motor delays) and 46.7% (cognitive abnormalities)., Conclusion: Our findings further expand the genetic mutation spectrum of biallelic MCM3AP and highlight the genotype-phenotype associations. Additionally, we elaborate on the importance of rehabilitation intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Xie, Hu, Xiang, Zhao, Chen and Zheng.)

We report an 8-year-old boy diagnosed with both CMT1 and narcolepsy, which were not reported simultaneously presenting in one person. The boy presented with a history of increased suddenly falling frequency and excessive daytime sleepiness for 3 months. CMT1 was diagnosed by electrophysiology and genetic testing. Narcolepsy had not been diagnosed until the frequently falling caused by sudden and transient episodes of legs weakness triggered by emotion was found. Multiple sleep latency test showed multiple sleep onset REM periods with reduced sleep latency. When CMT1 and narcolepsy were coexist in an individual, the latter might be overlooked. Cataplexy caused by narcolepsy might be disregard as distal muscle weakness of CMT1. The daytime sleepiness might also be ignored. Therefore, we recommend that patients with sleep disorders should be queried about the symptoms of narcolepsy.