PRICKLE2 revisited-further evidence implicating PRICKLE2 in neurodevelopmental disorders.
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:
08 2021
08 2021
Historique:
received:
27
01
2021
accepted:
18
05
2021
revised:
27
03
2021
pubmed:
8
6
2021
medline:
17
3
2022
entrez:
7
6
2021
Statut:
ppublish
Résumé
PRICKLE2 encodes a member of a highly conserved family of proteins that are involved in the non-canonical Wnt and planar cell polarity signaling pathway. Prickle2 localizes to the post-synaptic density, and interacts with post-synaptic density protein 95 and the NMDA receptor. Loss-of-function variants in prickle2 orthologs cause seizures in flies and mice but evidence for the role of PRICKLE2 in human disease is conflicting. Our goal is to provide further evidence for the role of this gene in humans and define the phenotypic spectrum of PRICKLE2-related disorders. We report a cohort of six subjects from four unrelated families with heterozygous rare PRICKLE2 variants (NM_198859.4). Subjects were identified through an international collaboration. Detailed phenotypic and genetic assessment of the subjects were carried out and in addition, we assessed the variant pathogenicity using bioinformatic approaches. We identified two missense variants (c.122 C > T; p.(Pro41Leu), c.680 C > G; p.(Thr227Arg)), one nonsense variant (c.214 C > T; p.(Arg72*) and one frameshift variant (c.1286_1287delGT; p.(Ser429Thrfs*56)). While the p.(Ser429Thrfs*56) variant segregated with disease in a family with three affected females, the three remaining variants occurred de novo. Subjects shared a mild phenotype characterized by global developmental delay, behavioral difficulties ± epilepsy, autistic features, and attention deficit hyperactive disorder. Computational analysis of the missense variants suggest that the altered amino acid residues are likely to be located in protein regions important for function. This paper demonstrates that PRICKLE2 is involved in human neuronal development and that pathogenic variants in PRICKLE2 cause neurodevelopmental delay, behavioral difficulties and epilepsy in humans.
Identifiants
pubmed: 34092786
doi: 10.1038/s41431-021-00912-y
pii: 10.1038/s41431-021-00912-y
pmc: PMC8385026
doi:
Substances chimiques
Codon, Nonsense
0
LIM Domain Proteins
0
Membrane Proteins
0
PRICKLE2 protein, human
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1235-1244Informations de copyright
© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.
Références
Katoh M, Katoh M. Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle. Int J Mol Med. 2003;11:249–56.
pubmed: 12525887
Tree DR, Shulman JM, Rousset R, Scott MP, Gubb D, Axelrod JD. Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell. 2002;109:371–81.
doi: 10.1016/S0092-8674(02)00715-8
Hida Y, Fukaya M, Hagiwara A, Deguchi-Tawarada M, Yoshioka T, Kitajima I, et al. Prickle2 is localized in the postsynaptic density and interacts with PSD-95 and NMDA receptors in the brain. J Biochem. 2011;149:693–700.
doi: 10.1093/jb/mvr023
Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, et al. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet. 2008;83:572–81.
doi: 10.1016/j.ajhg.2008.10.003
Paemka L, Mahajan VB, Skeie JM, Sowers LP, Ehaideb SN, Gonzalez-Alegre P, et al. PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. PLoS ONE. 2013;8:e80737.
doi: 10.1371/journal.pone.0080737
Bosoi CM, Capra V, Allache R, Trinh VQ, De Marco P, Merello E, et al. Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects. Hum Mutat. 2011;32:1371–5.
doi: 10.1002/humu.21589
Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, et al. Mutations in prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet. 2011;88:138–49.
doi: 10.1016/j.ajhg.2010.12.012
Bird TD, Shaw CM. Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 1978;41:140–9.
doi: 10.1136/jnnp.41.2.140
Sandford E, Bird TD, Li JZ, Burmeister M. PRICKLE2 Mutations Might Not Be Involved in Epilepsy. Am J Hum Genet. 2016;98:588–9.
doi: 10.1016/j.ajhg.2016.01.009
Sowers LP, Loo L, Wu Y, Campbell E, Ulrich JD, Wu S, et al. Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction. Mol Psychiatry. 2013;18:1077–89.
doi: 10.1038/mp.2013.71
Okumura A, Yamamoto T, Miyajima M, Shimojima K, Kondo S, Abe S, et al. 3p interstitial deletion including PRICKLE2 in identical twins with autistic features. Pediatr Neurol. 2014;51:730–3.
doi: 10.1016/j.pediatrneurol.2014.07.025
Sobreira N, Schiettecatte F, Valle D, Hamosh A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36:928–30.
doi: 10.1002/humu.22844
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.
doi: 10.1038/nmeth0410-248
Farheen N, Sen N, Nair S, Tan KP, Madhusudhan MS. Depth dependent amino acid substitution matrices and their use in predicting deleterious mutations. Prog Biophys Mol Biol. 2017;128:14–23.
doi: 10.1016/j.pbiomolbio.2017.02.004
Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019;47:D886–D94.
doi: 10.1093/nar/gky1016
Higgins DG, Sharp PM. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene 1988;73:237–44.
doi: 10.1016/0378-1119(88)90330-7
Striano S, Capovilla G, Sofia V, Romeo A, Rubboli G, Striano P, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia. 2009;50:15–9.
doi: 10.1111/j.1528-1167.2009.02114.x
Mastrangelo M, Tolve M, Martinelli M, Di Noia SP, Parrini E, Leuzzi V. PRICKLE1-related early onset epileptic encephalopathy. Am J Med Genet A. 2018;176:2841–5.
doi: 10.1002/ajmg.a.40625
Sweeney JA, Kmiec JA, Kupfer DJ. Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery. Biol Psychiatry. 2000;48:674–84.
doi: 10.1016/S0006-3223(00)00910-0
Mowlds W, Shannon C, McCusker CG, Meenagh C, Robinson D, Wilson A, et al. Autobiographical memory specificity, depression, and trauma in bipolar disorder. Br J Clin Psychol. 2010;49:217–33.
doi: 10.1348/014466509X454868
Kremers IP, Spinhoven P, Van der Does AJ. Autobiographical memory in depressed and non-depressed patients with borderline personality disorder. Br J Clin Psychol. 2004;43:17–29.
doi: 10.1348/014466504772812940
Gardner BK, O’Connor DW. A review of the cognitive effects of electroconvulsive therapy in older adults. J ECT. 2008;24:68–80.
doi: 10.1097/YCT.0b013e318165c7b0
Tielkes CE, Comijs HC, Verwijk E, Stek ML. The effects of ECT on cognitive functioning in the elderly: a review. Int J Geriatr Psychiatry. 2008;23:789–95.
doi: 10.1002/gps.1989
Bosboom PR, Deijen JB. Age-related cognitive effects of ECT and ECT-induced mood improvement in depressive patients. Depress Anxiety. 2006;23:93–101.
doi: 10.1002/da.20144
Sprock J, Rader TJ, Kendall JP, Yoder CY. Neuropsychological functioning in patients with borderline personality disorder. J Clin Psychol. 2000;56:1587–600.
doi: 10.1002/1097-4679(200012)56:12<1587::AID-9>3.0.CO;2-G