Genotype-phenotype correlations and effect of mutation location in Japanese CADASIL patients.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
29
11
2019
accepted:
11
03
2020
revised:
06
02
2020
pubmed:
12
4
2020
medline:
18
11
2020
entrez:
12
4
2020
Statut:
ppublish
Résumé
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by NOTCH3, and characterized by recurrent cerebral ischemic events without vascular risk factors, mood disturbance, and dementia. MRI testing shows cerebral white matter hyperintensities, especially in the external capsule and temporal pole. Typical mutations are cysteine-related missense ones located in one of 34 EGF-like repeats (EGFr) in the NOTCH3 receptor. To identify genotype-phenotype correlations, 179 Japanese CADASIL probands were recruited. Of the 68 mutations identified, p.Cys388Arg, p.Cys435Phe, p.Gly481Cys, p.Cys743Tyr, and p.Cys1009Phe were novel ones. The genotype-phenotype correlation was analyzed based on the three most common mutations: p.Arg75Pro, p.Arg141Cys, and p.Arg182Cys. p.Arg141Cys showed typical CADASIL phenotypes, whereas p.Arg75Pro showed mild and atypical phenotypes, a low frequency of stroke/TIA, high frequency of hypertension, and low frequency of temporal pole lesions. p.Arg182Cys showed various initial symptoms other than stroke/TIA. Subsequently, we analyzed the effect of the mutation location on the age at onset of stroke/TIA. We found that mutations in EGFr 1-6 excluding the cysteine-sparing mutation p.Arg75Pro were significantly correlated with a younger age at onset of stroke/TIA compared with those in EGFr 7-34. This was in agreement with a recent European report, suggesting that the effect of the mutation location is a consensus finding in CADASIL worldwide.
Identifiants
pubmed: 32277177
doi: 10.1038/s10038-020-0751-9
pii: 10.1038/s10038-020-0751-9
doi:
Substances chimiques
NOTCH3 protein, human
0
Receptor, Notch3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
637-646Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : 17ek0109130s0703
Références
Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009;8:643–53.
doi: 10.1016/S1474-4422(09)70127-9
Baudrimont M, Dubas F, Joutel A, Tournier-Lasserve E, Bousser MG. Autosomal dominant leukoencephalopathy and subcortical ischemic stroke. A clinicopathological study. Stroke. 1993;24:122–5.
doi: 10.1161/01.STR.24.1.122
Wang T, Baron M, Trump D. An overview of Notch3 function in vascular smooth muscle cells. Prog Biophys Mol Biol. 2008;96:499–509.
doi: 10.1016/j.pbiomolbio.2007.07.006
Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssiere C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet. 1997;350:1511–5.
doi: 10.1016/S0140-6736(97)08083-5
Duering M, Karpinska A, Rosner S, Hopfner F, Zechmeister M, Peters N, et al. Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis. Hum Mol Genet. 2011;20:3256–65.
doi: 10.1093/hmg/ddr237
Kim Y, Choi EJ, Choi CG, Kim G, Choi JH, Yoo HW, et al. Characteristics of CADASIL in Korea: a novel cysteine-sparing Notch3 mutation. Neurology. 2006;66:1511–6.
doi: 10.1212/01.wnl.0000216259.99811.50
Mizuno T, Muranishi M, Torugun T, Tango H, Nagakane Y, Kudeken T, et al. Two Japanese CADASIL families exhibiting Notch3 mutation R75P not involving cysteine residue. Intern Med. 2008;47:2067–72.
doi: 10.2169/internalmedicine.47.1391
Ueda A, Ueda M, Nagatoshi A, Hirano T, Ito T, Arai N, et al. Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014. J Neurol. 2015;262:1828–36.
doi: 10.1007/s00415-015-7782-8
Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004;127:2533–9.
doi: 10.1093/brain/awh282
Watanabe M, Adachi Y, Jackson M, Yamamoto-Watanabe Y, Wakasaya Y, Shirahama I, et al. An unusual case of elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple cerebrovascular risk factors. J Stroke Cerebrovasc Dis. 2012;21:143–5.
doi: 10.1016/j.jstrokecerebrovasdis.2010.05.008
Mizuta I, Watanabe-Hosomi A, Koizumi T, Mukai M, Hamano A, Tomii Y, et al. New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan. J Neurol Sci. 2017;381:62–7.
doi: 10.1016/j.jns.2017.08.009
Rutten JW, Haan J, Terwindt GM, van Duinen SG, Boon EM, Lesnik Oberstein SA. Interpretation of NOTCH3 mutations in the diagnosis of CADASIL. Expert Rev Mol Diagn. 2014;14:593–603.
doi: 10.1586/14737159.2014.922880
Liao YC, Hsiao CT, Fuh JL, Chern CM, Lee WJ, Guo YC, et al. Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles. PLoS ONE. 2015;10:e0136501.
doi: 10.1371/journal.pone.0136501
Kim YE, Yoon CW, Seo SW, Ki CS, Kim YB, Kim JW, et al. Spectrum of NOTCH3 mutations in Korean patients with clinically suspicious cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Neurobiol Aging. 2014;35:726 e1–6.
doi: 10.1016/j.neurobiolaging.2013.09.004
Rutten JW, Van Eijsden BJ, Duering M, Jouvent E, Opherk C, Pantoni L, et al. The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant. Genet Med. 2019;21:676–82.
doi: 10.1038/s41436-018-0088-3
Koizumi T, Mizuta I, Watanabe-Hosomi A, Mukai M, Hamano A, Matsuura J, et al. The CADASIL Scale-J, A Modified Scale to Prioritize Access to Genetic Testing for Japanese CADASIL-Suspected Patients. J Stroke Cerebrovasc Dis. 2019;28:1431–9.
doi: 10.1016/j.jstrokecerebrovasdis.2019.03.026
Takeshi Y, Suda S, Shimoyama T, Aoki J, Suzuki K, Okubo S, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy associated with a novel in-frame mutation in the NOTCH3 gene in a Japanese patient. J Stroke Cerebrovasc Dis. 2019;104482. https://doi.org/10.1016/j.jstrokecerebrovasdi .
Kunii M, Doi H, Ishii Y, Ohba C, Tanaka K, Tada M, et al. Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel. Clin Genet. 2018;94:232–8.
doi: 10.1111/cge.13371
Ebihara Y, Mochizuki H, Ishii N, Mizuta I, Shiomi K, Mizuno T, et al. A Japanese Case of CADASIL with a Rare Mutation in Exon 24 of the NOTCH3 Gene. Intern Med. 2018;57:3011–4.
doi: 10.2169/internalmedicine.0723-17
Mukai M, Mizuta I, Ueda A, Nakashima D, Kushimura Y, Noto YI, et al. A Japanese CADASIL patient with homozygous NOTCH3 p.Arg544Cys mutation confirmed pathologically. J Neurol Sci. 2018;394:38–40.
doi: 10.1016/j.jns.2018.08.029
Rutten JW, Dauwerse HG, Gravesteijn G, van Belzen MJ, van der Grond J, Polke JM, et al. Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL. Ann Clin Transl Neurol. 2016;3:844–53.
doi: 10.1002/acn3.344
Lee JS, Ko K, Oh JH, Park JH, Lee HK. Phenotypic features of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy subjects with R544C mutation. Dement Neurocogn Disord. 2016;15:15–9.
doi: 10.12779/dnd.2016.15.1.15
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.
doi: 10.1038/nature19057
Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.
doi: 10.1038/nature15393
Tadaka S, Katsuoka F, Ueki M, Kojima K, Makino S, Saito S, et al. 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome. Hum Genome Var. 2019;6:28.
doi: 10.1038/s41439-019-0059-5
Tadaka S, Saigusa D, Motoike IN, Inoue J, Aoki Y, Shirota M, et al. jMorp: Japanese Multi Omics Reference Panel. Nucleic Acids Res. 2018;46:D551–D7.
doi: 10.1093/nar/gkx978
Narayan SK, Gorman G, Kalaria RN, Ford GA, Chinnery PF. The minimum prevalence of CADASIL in northeast England. Neurology. 2012;78:1025–7.
doi: 10.1212/WNL.0b013e31824d586c
Razvi SS, Davidson R, Bone I, Muir KW. The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland. J Neurol Neurosurg Psychiatry. 2005;76:739–41.
doi: 10.1136/jnnp.2004.051847
Bianchi S, Zicari E, Carluccio A, Di Donato I, Pescini F, Nannucci S, et al. CADASIL in central Italy: a retrospective clinical and genetic study in 229 patients. J Neurol. 2015;262:134–41.
doi: 10.1007/s00415-014-7533-2