A biallelic variant of DCAF13 implicated in a neuromuscular disorder in humans.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
29
08
2022
accepted:
09
02
2023
revised:
05
02
2023
pmc-release:
01
06
2024
medline:
12
6
2023
pubmed:
17
2
2023
entrez:
16
2
2023
Statut:
ppublish
Résumé
Neuromuscular disorders encompass a broad range of phenotypes and genetic causes. We investigated a consanguineous family in which multiple patients had a neuromuscular disorder characterized by a waddling gait, limb deformities, muscular weakness and facial palsy. Exome sequencing was completed on the DNA of three of the four patients. We identified a novel missense variant in DCAF13, ENST00000612750.5, NM_015420.7, c.907 G > A;p.(Asp303Asn), ENST00000616836.4, NM_015420.6, c.1363 G > A:p.(Asp455Asn) (rs1209794872) segregating with this phenotype; being homozygous in all four affected patients and heterozygous in the unaffected individuals. The variant was extremely rare in the public databases (gnomAD allele frequency 0.000007081); was absent from the DNA of 300 ethnically matched controls and affected an amino acid which has been conserved across 1-2 billion years of evolution in eukaryotes. DCAF13 contains three WD40 domains and is hypothesized to have roles in both rRNA processing and in ubiquitination of proteins. Analysis of DCAF13 with the p.(Asp455Asn) variant predicted that the amino acid change is deleterious and affects a β-hairpin turn, within a WD40 domain of the protein which may decrease protein stability. Previously, a heterozygous variant of DCAF13 NM_015420.6, c.20 G > C:p.(Trp7Ser) with or without a heterozygous missense variant in CCN3, was suggested to cause inherited cortical myoclonic tremor with epilepsy. In addition, a heterozygous DCAF13 variant has been associated with autism spectrum disorder. Our study indicates a potential role of biallelic DCAF13 variants in neuromuscular disorders. Screening of additional patients with similar phenotype may broaden the allelic and phenotypic spectrum due to DCAF13 variants.
Identifiants
pubmed: 36797467
doi: 10.1038/s41431-023-01319-7
pii: 10.1038/s41431-023-01319-7
pmc: PMC10250411
doi:
Substances chimiques
DCAF13 protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
629-637Subventions
Organisme : Higher Education Commision, Pakistan (Pakistani Higher Education Commission)
ID : 2877
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.
Références
Cell Death Differ. 2019 Jul;26(7):1251-1266
pubmed: 30283081
J Cell Biol. 2019 Mar 4;218(3):993-1010
pubmed: 30670470
Nat Rev Neurol. 2017 Nov;13(11):647-661
pubmed: 28960187
Nat Commun. 2021 Mar 25;12(1):1879
pubmed: 33767194
Crit Rev Clin Lab Sci. 2012 Mar-Apr;49(2):33-48
pubmed: 22468856
EMBO J. 2018 Sep 14;37(18):
pubmed: 30111536
J Neuromuscul Dis. 2015;2(1):73-85
pubmed: 28198707
Neurosci Lett. 2018 Sep 25;684:115-120
pubmed: 30003937
Protein Cell. 2011 Mar;2(3):202-14
pubmed: 21468892
Mol Cell. 2006 Sep 1;23(5):709-21
pubmed: 16949367
Tumour Biol. 2017 Jun;39(6):1010428317705753
pubmed: 28631558
Front Mol Neurosci. 2019 Nov 01;12:262
pubmed: 31736708
MicroPubl Biol. 2022 Sep 23;2022:
pubmed: 36217444
Lancet Child Adolesc Health. 2018 Aug;2(8):600-609
pubmed: 30119719
Cold Spring Harb Mol Case Stud. 2016 Nov;2(6):a001172
pubmed: 27900362
Clin Genet. 2016 Sep;90(3):263-9
pubmed: 26612766
Carbohydr Res. 2009 Mar 10;344(4):491-500
pubmed: 19185293
Curr Genomics. 2018 May;19(4):300-312
pubmed: 29755292
Neuromuscul Disord. 1991;1(1):19-29
pubmed: 1822774
Proteins. 2009 Nov 15;77(3):491-8
pubmed: 19626709
Genome Biol. 2007;8(10):R215
pubmed: 17925008
Nat Rev Drug Discov. 2017 Nov;16(11):773-786
pubmed: 29026209
Bioinformatics. 2014 May 1;30(9):1312-3
pubmed: 24451623
Nat Protoc. 2010 Apr;5(4):725-38
pubmed: 20360767
Trends Genet. 2011 Sep;27(9):377-86
pubmed: 21764165
Bioessays. 2021 Jul;43(7):e2100057
pubmed: 33857330
Int J Mol Sci. 2013 Jul 24;14(8):15286-311
pubmed: 23887652
Hum Mutat. 2013 Jan;34(1):50-6
pubmed: 23090942
Neurology. 2014 Mar 11;82(10):873-8
pubmed: 24500646
Am J Hum Genet. 2013 Aug 8;93(2):249-63
pubmed: 23849776
Nat Genet. 1997 Jan;15(1):70-3
pubmed: 8988171
J Med Genet. 2015 Mar;52(3):208-16
pubmed: 25635128
Nucleic Acids Res. 2001 Sep 1;29(17):E88-8
pubmed: 11522844
BMC Genomics. 2020 Aug 31;21(1):602
pubmed: 32867693
Front Mol Neurosci. 2018 Dec 04;11:448
pubmed: 30568575
Bioinformatics. 2012 Jun 15;28(12):1647-9
pubmed: 22543367
Biopolymers. 2008 May;89(5):380-91
pubmed: 18275088
Genes (Basel). 2021 Jun 16;12(6):
pubmed: 34208743
Nat Ecol Evol. 2018 Oct;2(10):1556-1562
pubmed: 30127539
Clin Exp Dermatol. 2020 Mar;45(2):159-164
pubmed: 31323129
Circ Genom Precis Med. 2018 Jan;11(1):e001758
pubmed: 29874175
Sci Rep. 2019 Apr 18;9(1):6278
pubmed: 31000741
Biochem Cell Biol. 2014 Jun;92(3):191-9
pubmed: 24754225
Bone. 2010 Sep;47(3):636-42
pubmed: 20601284
Int J Cell Biol. 2014;2014:217371
pubmed: 24799906
Orthop Traumatol Surg Res. 2018 Feb;104(1S):S89-S95
pubmed: 29196274
Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
pubmed: 15034147