Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

H. Kolarova, J. Tan, TM. Strom, T. Meitinger, M. Wagner, T. Klopstock

. 2022 ; 77 (-) : 103869. [pub] 20220215

Language English Country Netherlands

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc22019267

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 (>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. FUNDING: This work was carried out in the framework of TIRCON ("Treat Iron-Related Childhood-Onset Neurodegeneration").

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22019267
003      
CZ-PrNML
005      
20220804135503.0
007      
ta
008      
220720s2022 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.ebiom.2022.103869 $2 doi
035    __
$a (PubMed)35180557
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Kolarova, Hana $u Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig Maximilian University of Munich, Ziemssenstraße 1a, Munich 80336, Germany; Institute of Human Genetics, Technical University of Munich, Trogerstraße 32, Munich 81675, Germany; Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Ke Karlovu 2, Prague 12000, Czech Republic
245    10
$a Lifetime risk of autosomal recessive neurodegeneration with brain iron accumulation (NBIA) disorders calculated from genetic databases / $c H. Kolarova, J. Tan, TM. Strom, T. Meitinger, M. Wagner, T. Klopstock
520    9_
$a 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 (>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. FUNDING: This work was carried out in the framework of TIRCON ("Treat Iron-Related Childhood-Onset Neurodegeneration").
650    _2
$a mozek $x patologie $7 D001921
650    _2
$a proteiny vázající vápník $7 D002135
650    _2
$a dítě $7 D002648
650    _2
$a databáze genetické $7 D030541
650    _2
$a lidé $7 D006801
650    12
$a poruchy metabolismu železa $x genetika $x patologie $7 D019189
650    _2
$a mitochondriální proteiny $x genetika $7 D024101
650    12
$a neuroaxonální dystrofie $x epidemiologie $x genetika $x patologie $7 D019150
650    12
$a neurodegenerativní nemoci $x epidemiologie $x genetika $x patologie $7 D019636
650    _2
$a jaderné proteiny $7 D009687
650    _2
$a komplexy ubikvitinligas $7 D043743
655    _2
$a časopisecké články $7 D016428
700    1_
$a Tan, Jing $u Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig Maximilian University of Munich, Ziemssenstraße 1a, Munich 80336, Germany; Institute of Human Genetics, Technical University of Munich, Trogerstraße 32, Munich 81675, Germany; Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
700    1_
$a Strom, Tim M $u Institute of Human Genetics, Technical University of Munich, Trogerstraße 32, Munich 81675, Germany
700    1_
$a Meitinger, Thomas $u Institute of Human Genetics, Technical University of Munich, Trogerstraße 32, Munich 81675, Germany
700    1_
$a Wagner, Matias $u Institute of Human Genetics, Technical University of Munich, Trogerstraße 32, Munich 81675, Germany; Institute of Neurogenomics, Helmholtz Zentrum Munich, Ingolstädter Landstraße 1, Neuherberg 85764, Germany; LMU University Hospital, Department of Pediatrics, Dr. von Hauner Children's Hospital, Division of Pediatric Neurology, LMU Center for Development and Children with Medical Complexity, Ludwig-Maximilians-University, Munich, Germany. Electronic address: Matias.Wagner@mri.tum.de
700    1_
$a Klopstock, Thomas $u Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig Maximilian University of Munich, Ziemssenstraße 1a, Munich 80336, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address: Thomas.Klopstock@med.uni-muenchen.de
773    0_
$w MED00190061 $t EBioMedicine $x 2352-3964 $g Roč. 77, č. - (2022), s. 103869
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35180557 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220720 $b ABA008
991    __
$a 20220804135457 $b ABA008
999    __
$a ok $b bmc $g 1822740 $s 1170510
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 77 $c - $d 103869 $e 20220215 $i 2352-3964 $m EBioMedicine $n EBioMedicine $x MED00190061
LZP    __
$a Pubmed-20220720

Find record

Citation metrics

Archiving options