Lifetime risk of autosomal recessive neurodegeneration with brain iron accumulation (NBIA) disorders calculated from genetic databases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10445225" target="_blank" >RIV/00064165:_____/22:10445225 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/22:10445225

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=UE5Zql8ft5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=UE5Zql8ft5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ebiom.2022.103869" target="_blank" >10.1016/j.ebiom.2022.103869</a>

Result language

angličtina

Original language name

Lifetime risk of autosomal recessive neurodegeneration with brain iron accumulation (NBIA) disorders calculated from genetic databases

Original language description

Background: Neurodegeneration with brain iron accumulation (NBIA) are a group of clinically and genetically heterogeneous diseases characterized by iron overload in basal ganglia and progressive neurodegeneration. Little is known about the epidemiology of NBIA disorders. In the absence of large-scale population-based studies, obtaining reliable epidemiological data requires innovative approaches. Methods: All pathogenic variants were collected from the 13 genes associated with autosomal recessive NBIA (PLA2G6, PANK2, COASY, ATP13A2, CP, AP4M1, FA2H, CRAT, SCP2, C19orf12, DCAF17, GTPBP2, REPS1). The allele frequencies of these disease-causing variants were assessed in exome/genome collections: the Genome Aggregation Database (gnomAD) and our in-house database. Lifetime risks were calculated from the sum of allele frequencies in the respective genes under assumption of Hardy-Weinberg equilibrium. Findings: The combined estimated lifetime risk of all 13 investigated NBIA disorders is 0.88 (95% confidence interval 0.70–1.10) per 100,000 based on the global gnomAD dataset (n = 282,912 alleles), 0.92 (0.65–1.29) per 100,000 in the European gnomAD dataset (n = 129,206), and 0.90 (0.48–1.62) per 100,000 in our in-house database (n = 44,324). Individually, the highest lifetime risks (&gt;0.15 per 100,000) are found for disorders caused by variants in PLA2G6, PANK2 and COASY. Interpretation: This population-genetic estimation on lifetime risks of recessive NBIA disorders reveals frequencies far exceeding previous population-based numbers. Importantly, our approach represents lifetime risks from conception, thus including prenatal deaths. Understanding the true lifetime risk of NBIA disorders is important in estimating disease burden, allocating resources and targeting specific interventions.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30101 - Human genetics

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

EBioMedicine [online]

ISSN

2352-3964

e-ISSN

—

Volume of the periodical

77

Issue of the periodical within the volume

March

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

103869

UT code for WoS article

000819469500002

EID of the result in the Scopus database

2-s2.0-85124550390