Abstract
Niemann–Pick type C (NP-C) disease is an autosomal recessive disease caused by variants in the NPC1 or NPC2 genes. It has a large range of symptoms depending on age of onset, thus making it difficult to diagnose. In adults, symptoms appear mainly in the form of psychiatric problems. The prevalence varies from 0.35 to 2.2 per 100,000 births depending on the country. The aim of this study is to calculate the estimated prevalence of NP-C in Quebec to determine if it is underdiagnosed in this population. The CARTaGENE database is a unique database that regroups individuals between 40 and 69 years old from metropolitan regions of Quebec. RNA-sequencing data was available for 911 individuals and exome sequencing for 198 individuals. We used a bioinformatic pipeline on those individuals to extract the variants in the NPC1/2 genes. The prevalence in Quebec was estimated assuming Hardy–Weinberg Equilibrium. Two pathogenic variants were used. The variant p.Pro543Leu was found in three heterozygous individuals that share a common haplotype, which suggests a founder French-Canadian pathogenic variant. The variant p.Ile1061Thr was found in two heterozygous individuals. Both variants have previously been reported and are usually associated with infantile onset. The estimated prevalence calculated using those two variants is 0.61:100,000 births. This study represents the first estimate of NP-C in Quebec. The estimated prevalence for NP-C is likely underestimated due to misdiagnosis or missed cases. It is therefore important to diagnose all NP-C patients to initiate early treatment.
Highlights
Niemann–Pick type C (NP-C) disease is an autosomal recessive disease caused by variants in the NPC1 or NPC2 genes
NP-C is caused by pathogenic variants in the NPC1 gene (NM_000271) in 95% of cases and the rest is due to pathogenic variants in the NPC2 gene (NM_006432)[5]
In the CaG cohort, we found two variants classified as pathogenic in the NPC1 gene (Table 1)
Summary
Niemann–Pick type C (NP-C) disease is an autosomal recessive disease caused by variants in the NPC1 or NPC2 genes It has a large range of symptoms depending on age of onset, making it difficult to diagnose. Adult-onset subtypes have been reported and often present an atypical phenotype with psychiatric symptoms In some cases, it can mimic other neurodegenerative diseases such as Alzheimer, Wilson or P arkinson[6,7,8]. Considering the founder effect in the French-Canadian population, we want to explore how it may affect the prevalence of rare variants in NPC1 and NPC2 and, of the NP-C disease. It was developed to help study diseases and the genetics of the Quebec population
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