Estimated prevalence of Niemann-Pick type C disease in Quebec.
Adult
Aged
Alleles
Cities
Computational Biology
Exome
Female
Gene Frequency
Genetic Variation
Genome, Human
Haplotypes
Heterozygote
Humans
Infant, Newborn
Male
Membrane Glycoproteins
/ genetics
Middle Aged
Niemann-Pick C1 Protein
/ genetics
Niemann-Pick Disease, Type C
/ epidemiology
Prevalence
Quebec
RNA-Seq
Vesicular Transport Proteins
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 11 2021
19 11 2021
Historique:
received:
11
08
2021
accepted:
08
11
2021
entrez:
20
11
2021
pubmed:
21
11
2021
medline:
8
3
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34799641
doi: 10.1038/s41598-021-01966-0
pii: 10.1038/s41598-021-01966-0
pmc: PMC8604933
doi:
Substances chimiques
Membrane Glycoproteins
0
NPC1 protein, human
0
NPC2 protein, human
0
Niemann-Pick C1 Protein
0
Vesicular Transport Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22621Informations de copyright
© 2021. The Author(s).
Références
Evans, W. R. & Hendriksz, C. J. Niemann–Pick type C disease–the tip of the iceberg? A review of neuropsychiatric presentation, diagnosis and treatment. BJPsych Bull. 41(2), 109–114 (2017).
pubmed: 28400970
pmcid: 5376728
doi: 10.1192/pb.bp.116.054072
Wraith, J. E. Lysosomal disorders. Semin Neonatol. 7(1), 75–83 (2002).
pubmed: 12069540
doi: 10.1053/siny.2001.0088
Poorthuis, B. J. et al. The frequency of lysosomal storage diseases in The Netherlands. Hum. Genet. 105(1–2), 151–156 (1999).
pubmed: 10480370
doi: 10.1007/s004399900075
Pinto, R. et al. Prevalence of lysosomal storage diseases in Portugal. Eur. J. Hum. Genet. 12(2), 87–92 (2004).
pubmed: 14685153
doi: 10.1038/sj.ejhg.5201044
Vanier, M. T. Niemann–Pick disease type C. Orphanet J. Rare Dis. 5(1), 16 (2010).
pubmed: 20525256
pmcid: 2902432
doi: 10.1186/1750-1172-5-16
Malnar, M. et al. Bidirectional links between Alzheimer’s disease and Niemann–Pick type C disease. Neurobiol. Dis. 72, 37–47 (2014).
pubmed: 24907492
doi: 10.1016/j.nbd.2014.05.033
Sakiyama, Y. et al. Abnormal copper metabolism in Niemann–Pick disease type C mimicking Wilson’s disease. Neurol. Clin. Neurosci. 2(6), 193–200 (2014).
doi: 10.1111/ncn3.122
Zavala, L., et al., Niemann Pick type C as presentation of Huntington-like syndrome (P4. 043). AAN Enterprises (2018).
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581(7809), 434–443 (2020).
pubmed: 32461654
pmcid: 7334197
doi: 10.1038/s41586-020-2308-7
Patterson, M., Niemann–Pick disease type C. GeneReviews®[Internet] (2019).
Tétreault, M. et al. Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation. Brain J. Neurol. 138(Pt 6), 1477–1483 (2015).
doi: 10.1093/brain/awv074
Bras, J., Guerreiro, R. & Hardy, J. Use of next-generation sequencing and other whole-genome strategies to dissect neurological disease. Nat. Rev. Neurosci. 13(7), 453–464 (2012).
pubmed: 22714018
doi: 10.1038/nrn3271
Schneider, S.A., et al., Do heterozygous mutations of Niemann–Pick type C predispose to late-onset neurodegeneration: A review of the literature. J. Neurol., 2019: 1–10.
Bremova-Ertl, T. et al. Clinical, ocular motor, and imaging profile of Niemann–Pick type C heterozygosity. Neurology 94(16), e1702 (2020).
pubmed: 32234823
doi: 10.1212/WNL.0000000000009290
Poupětová, H. et al. The birth prevalence of lysosomal storage disorders in the Czech Republic: Comparison with data in different populations. J. Inherit. Metab. Dis. 33(4), 387–396 (2010).
pubmed: 20490927
pmcid: 2903693
doi: 10.1007/s10545-010-9093-7
Laberge, A. M. et al. Population history and its impact on medical genetics in Quebec. Clin. Genet. 68(4), 287–301 (2005).
pubmed: 16143014
doi: 10.1111/j.1399-0004.2005.00497.x
Bchetnia, M., et al., Genetic burden linked to founder effects in Saguenay-Lac-Saint-Jean illustrates the importance of genetic screening test availability. J. Med. Genetics, 2021.
Roy-Gagnon, M.-H. et al. Genomic and genealogical investigation of the French Canadian founder population structure. Hum. Genet. 129(5), 521–531 (2011).
pubmed: 21234765
doi: 10.1007/s00439-010-0945-x
Winsor, E. & Welch, J. Genetic and demographic aspects of Nova Scotia Niemann–Pick disease (type D). Am. J. Hum. Genet. 30(5), 530 (1978).
pubmed: 736041
pmcid: 1685594
Greer, W. L. et al. The Nova Scotia (type D) form of Niemann–Pick disease is caused by a G3097–>T transversion in NPC1. Am. J. Hum. Genet. 63(1), 52–54 (1998).
pubmed: 9634529
pmcid: 1377252
doi: 10.1086/301931
Awadalla, P. et al. Cohort profile of the CARTaGENE study: Quebec’s population-based biobank for public health and personalized genomics. Int. J. Epidemiol. 42(5), 1285–1299 (2012).
pubmed: 23071140
doi: 10.1093/ije/dys160
Touma, L. et al. Identification and classification of rare variants in NPC1 and NPC2 in Quebec. Sci. Rep. 11(1), 10344 (2021).
pubmed: 33990640
pmcid: 8121778
doi: 10.1038/s41598-021-89630-5
Hussin, J. G. et al. Recombination affects accumulation of damaging and disease-associated mutations in human populations. Nat. Genet. 47(4), 400–404 (2015).
pubmed: 25685891
doi: 10.1038/ng.3216
Frésard, L. et al. Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts. Nat. Med. 25(6), 911–919 (2019).
pubmed: 31160820
pmcid: 6634302
doi: 10.1038/s41591-019-0457-8
Gonorazky, H. D. et al. Expanding the boundaries of RNA sequencing as a diagnostic tool for rare mendelian disease. Am. J. Hum. Genet. 104(3), 466–483 (2019).
pubmed: 30827497
pmcid: 6407525
doi: 10.1016/j.ajhg.2019.01.012
Nicolau, S. et al. A molecular diagnosis of LGMDR1 established by RNA sequencing. Can. J. Neurol. Sci. 48(2), 293–296 (2021).
pubmed: 32646536
doi: 10.1017/cjn.2020.141
Vasli, N. et al. Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion. Brain J. Neurol. 140(1), 37–48 (2017).
doi: 10.1093/brain/aww257
Kim, D. et al. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37(8), 907–915 (2019).
pubmed: 31375807
pmcid: 7605509
doi: 10.1038/s41587-019-0201-4
Lai, Z. et al. VarDict: A novel and versatile variant caller for next-generation sequencing in cancer research. Nucleic Acids Res. 44(11), e108–e108 (2016).
pubmed: 27060149
pmcid: 4914105
doi: 10.1093/nar/gkw227
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25(14), 1754–1760 (2009).
pubmed: 19451168
pmcid: 2705234
doi: 10.1093/bioinformatics/btp324
McKenna, A. et al. The genome analysis toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20(9), 1297–1303 (2010).
pubmed: 20644199
pmcid: 2928508
doi: 10.1101/gr.107524.110
Wang, K., Li, M. & Hakonarson, H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38(16), e164–e164 (2010).
pubmed: 20601685
pmcid: 2938201
doi: 10.1093/nar/gkq603
Rentzsch, P. et al. CADD: Predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 47(D1), D886–D894 (2019).
pubmed: 30371827
doi: 10.1093/nar/gky1016
Ng, P. C. & Henikoff, S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 31(13), 3812–3814 (2003).
pubmed: 12824425
pmcid: 168916
doi: 10.1093/nar/gkg509
Adzhubei, I., Jordan, D. M. & Sunyaev, S. R. Predicting functional effect of human missense mutations using PolyPhen-2. Curr. Protoc. Hum. Genet. 76(1), 7–20 (2013).
Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15(8), 1034–1050 (2005).
pubmed: 16024819
pmcid: 1182216
doi: 10.1101/gr.3715005
Davydov, E. V. et al. Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput Biol 6(12), e1001025 (2010).
pubmed: 21152010
pmcid: 2996323
doi: 10.1371/journal.pcbi.1001025
Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17(5), 405–423 (2015).
pubmed: 25741868
pmcid: 4544753
doi: 10.1038/gim.2015.30
Millat, G. et al. Niemann–Pick C disease: Use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families. Mol. Genet. Metab. 86(1–2), 220–232 (2005).
pubmed: 16126423
doi: 10.1016/j.ymgme.2005.07.007
Thiffault, I. et al. Diversity of ARSACS mutations in French-Canadians. Can. J. Neurol. Sci. 40(1), 61–66 (2013).
pubmed: 23250129
doi: 10.1017/S0317167100012968
Millat, G. et al. Niemann–Pick C1 disease: The I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype. Am. J. Hum. Genet. 65(5), 1321–1329 (1999).
pubmed: 10521297
pmcid: 1288284
doi: 10.1086/302626
Québec, I.D.L.S.D., Le bilan démographique du Québec. Édition 2020 (2020) p. 183.
Fernandez-Valero, E. et al. Identification of 25 new mutations in 40 unrelated Spanish Niemann–Pick type C patients: Genotype-phenotype correlations. Clin. Genet. 68(3), 245–254 (2005).
pubmed: 16098014
doi: 10.1111/j.1399-0004.2005.00490.x
Meikle, P. J. et al. Prevalence of lysosomal storage disorders. JAMA 281(3), 249–254 (1999).
pubmed: 9918480
doi: 10.1001/jama.281.3.249
Imrie, J. et al. Observational cohort study of the natural history of Niemann–Pick disease type C in the UK: A 5-year update from the UK clinical database. BMC Neurol. 15, 257–257 (2015).
pubmed: 26666848
pmcid: 4678528
doi: 10.1186/s12883-015-0511-1
Wassif, C. A. et al. High incidence of unrecognized visceral/neurological late-onset Niemann–Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets. Genet. Med. 18(1), 41 (2016).
pubmed: 25764212
doi: 10.1038/gim.2015.25
Wraith, J. E. et al. Miglustat in adult and juvenile patients with Niemann–Pick disease type C: Long-term data from a clinical trial. Mol. Genet. Metab. 99(4), 351–357 (2010).
pubmed: 20045366
doi: 10.1016/j.ymgme.2009.12.006
Jiang, X. et al. A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann–Pick C1 disease from human plasma. J. Lipid Res. 52(7), 1435–1445 (2011).
pubmed: 21518695
pmcid: 3122908
doi: 10.1194/jlr.D015735
Wijburg, F. A. et al. Development of a suspicion index to aid diagnosis of Niemann–Pick disease type C. Neurology 78(20), 1560–1567 (2012).
pubmed: 22517094
doi: 10.1212/WNL.0b013e3182563b82
Québec, G.d. Blood and Urine Screening in Newborns. 2020; https://www.quebec.ca/en/health/advice-and-prevention/screening-and-carrier-testing-offer/blood-and-urine-screening-in-newborns/diseases-screened .
Polo, G. et al. High level of oxysterols in neonatal cholestasis: A pitfall in analysis of biochemical markers for Niemann–Pick type C disease. CCLM 54(7), 1221–1229 (2016).
pubmed: 26650075
doi: 10.1515/cclm-2015-0669
Wasserstein, M. P. et al. The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants. Genet. Med. 21(3), 631–640 (2019).
pubmed: 30093709
doi: 10.1038/s41436-018-0129-y