Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report.
Genetic testing
Homozygous nonsense variant
Immotile-cilia syndrome
NEK10
Primary Ciliary dyskinesia
Respiratory issues
Journal
BMC pulmonary medicine
ISSN: 1471-2466
Titre abrégé: BMC Pulm Med
Pays: England
ID NLM: 100968563
Informations de publication
Date de publication:
15 May 2020
15 May 2020
Historique:
received:
16
01
2020
accepted:
29
04
2020
entrez:
17
5
2020
pubmed:
18
5
2020
medline:
17
2
2021
Statut:
epublish
Résumé
Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing. Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells. NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.
Sections du résumé
BACKGROUND
BACKGROUND
Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing.
CASE PRESENTATION
METHODS
Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells.
CONCLUSIONS
CONCLUSIONS
NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.
Identifiants
pubmed: 32414360
doi: 10.1186/s12890-020-1175-1
pii: 10.1186/s12890-020-1175-1
pmc: PMC7229615
doi:
Substances chimiques
NIMA-Related Kinases
EC 2.7.11.1
Nek10 protein, human
EC 2.7.11.1
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
141Subventions
Organisme : King Abdullah International Medical Research Center
ID : RC18/017/R
Références
Dis Model Mech. 2012 May;5(3):299-312
pubmed: 22566558
J Biol Chem. 2011 Apr 15;286(15):13502-11
pubmed: 21317289
Am J Hum Genet. 2011 Jan 7;88(1):106-14
pubmed: 21211617
Trends Cell Biol. 2003 May;13(5):221-8
pubmed: 12742165
J Am Soc Nephrol. 2008 Mar;19(3):587-92
pubmed: 18199800
Thorax. 2018 Feb;73(2):157-166
pubmed: 28790179
Cell. 2015 Apr 23;161(3):692-692.e1
pubmed: 25910215
Circulation. 2007 Jun 5;115(22):2814-21
pubmed: 17515466
Eur Respir J. 2014 Dec;44(6):1579-88
pubmed: 25186273
Development. 2002 Dec;129(24):5839-46
pubmed: 12421721
Acta Paediatr. 2002;91(6):667-9
pubmed: 12162599
Mol Biol Cell. 2006 Jun;17(6):2799-810
pubmed: 16611747
Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7786-91
pubmed: 27357676
Eur Respir J. 2017 Jan 4;49(1):
pubmed: 28052956
Cell Div. 2011 Oct 31;6:18
pubmed: 22040655
Mol Cell Biol. 2011 Jan;31(1):30-42
pubmed: 20956560
Cilia. 2015 Jan 22;4(1):2
pubmed: 25610612
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):217-21
pubmed: 10618398
J Cell Sci. 2005 Nov 15;118(Pt 22):5161-9
pubmed: 16280549
Nat Rev Neurol. 2014 Jan;10(1):27-36
pubmed: 24296655
Front Cell Dev Biol. 2017 Dec 01;5:102
pubmed: 29250521
Eur Respir J. 2009 Dec;34(6):1264-76
pubmed: 19948909
Trends Genet. 2011 Aug;27(8):307-15
pubmed: 21680046
Front Pediatr. 2017 Jun 09;5:135
pubmed: 28649564
Nat Commun. 2018 Mar 26;9(1):1224
pubmed: 29581457
Nat Med. 2020 Feb;26(2):300
pubmed: 31996837
J Cell Sci. 2012 Oct 1;125(Pt 19):4423-33
pubmed: 23132929
Paediatr Respir Rev. 2019 Feb;29:19-22
pubmed: 30792130