Journal
GENETICS IN MEDICINE
Volume 18, Issue 1, Pages 41-48Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gim.2015.25
Keywords
allele frequency; next-generation sequence study; Niemann-Pick disease; NPC; type C
Categories
Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Human Genome Research Institute intramural research programs, Department of Health and Human Services
- MRC
- Medical Research Council [MC_UU_12021/1, MC_U137761446] Funding Source: researchfish
- MRC [MC_U137761446, MC_UU_12021/1] Funding Source: UKRI
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [ZICHD008958, ZIAHD000139, ZIAHD008824] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZIAHG200387, ZIAHG200327, ZIAHG200359] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Purpose: Niemann-Pick disease type C (NPC) is a recessive, neurodegenerative, lysosomal storage disease caused by mutations in either NPC1 or NPC2. The diagnosis is difficult and frequently delayed. Ascertainment is likely incomplete because of both these factors and because the full phenotypic spectrum may not have been fully delineated. Given the recent development of a blood-based diagnostic test and the development of potential therapies, understanding the incidence of NPC and defining at-risk patient populations are important. Method: We evaluated data from four large, massively parallel exome sequencing data sets. Variant sequences were identified and classified as pathogenic or nonpathogenic based on a combination of literature review and bioinformatic analysis. This methodology provided an unbiased approach to determining the allele frequency. Results: Our data suggest an incidence rate for NPC1 and NPC2 of 1/92,104 and 1/2,858,998, respectively. Evaluation of common NPC1 variants, however, suggests that there may be a late-onset NPC1 phenotype with a markedly higher incidence, on the order of 1/19,0001/ 36,000. Conclusion: We determined a combined incidence of classical NPC of 1/89,229, or 1.12 affected patients per 100,000 conceptions, but predict incomplete ascertainment of a late-onset phenotype of NPC1. This finding strongly supports the need for increased screening of potential patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available