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@ARTICLE{BrmovErtl:280909,
author = {Brémovà-Ertl, Tatiana and Tahirovic, Sabina and Katušić
Hećimović, Silva and Martakis, Kyriakos and Rohrbach,
Marianne and Gautschi, Matthias and Dhamija, Radhika and
Ganesh, Jaya and Peters, Melinda and Walterfang, Mark and
Schneider, Susanne A},
title = {{H}eterozygosity in {NPC} may be associated with neurologic
and systemic phenotypes.},
journal = {Frontiers in neurology},
volume = {16},
issn = {1664-2295},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {DZNE-2025-00992},
pages = {1618380},
year = {2025},
abstract = {Niemann-Pick disease type C (NPC) is a pan-ethnic,
progressive, recessively inherited lysosomal disorder that
affects 1:100,000 live births. Emerging biochemical,
genetic, and clinical evidence challenges the traditional
view that disease-associated variants in the genes
associated with the typical phenotype NPC manifest as an
exclusively autosomal recessive disorder. While biallelic
pathogenic variants cause the NPC disease phenotype,
heterozygous carriers may exhibit phenotypic traits
attributable to a partial loss of NPC1 or NPC2 function.We
conducted a literature search of articles relevant to
heterozygosity in NPC genes and genes associated with other
lysosomal diseases. A narrative mini-review format was
employed with the intention of providing a brief overview of
the frequency of NPC carriers, as well as the biochemical,
genetic, non-clinical, and clinical evidence available for
readers seeking to understand the scientific basis for why
NPC heterozygosity should be discussed and considered as a
potential risk factor for the development of neurological
phenotype or neurodegenerative diseases.Heterozygosity for
many genes, including NPC1 variants, ('carriers' of a single
variant in an NPC gene) can be clinically consequential.
Recognizing the effects of NPC1 heterozygosity has profound
implications for diagnosis, clinical monitoring, and
potential early intervention. By broadening our
understanding of the genetic and phenotypic spectrum of NPC,
we can improve detection (which is straightforward in
obligate heterozygotes, i.e., parents of NPC patients),
reduce long-term health risks, and utilize targeted
treatments that address the needs of carriers as well as
affected individuals.},
subtyp = {Review Article},
keywords = {Niemann-Pick disease type C (Other) / carrier (Other) /
heterozygosity (Other) / heterozygote (Other) / rare disease
(Other)},
cin = {AG Tahirovic},
ddc = {610},
cid = {I:(DE-2719)1140003},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40874127},
pmc = {pmc:PMC12378043},
doi = {10.3389/fneur.2025.1618380},
url = {https://pub.dzne.de/record/280909},
}