Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene

Sun, Lin; Li, Xia; Lin, Xiang; Feng, Yue; Chen, Kathryn; Xiao, Shifu

doi:10.1080/19336896.2015.1054601

Cited by 13 publications

(9 citation statements)

References 17 publications

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“…There is no significant gender difference in the incidence of FFI. They both have typical clinical features similar to previous descriptions of FFI [16]. Sleep disturbances, such as insomnia and sleep loss, are the common foremost symptoms of the Chinese FFI patients.…”

Section: Discussionsupporting

confidence: 77%

Clinical features and genetic characteristics of two Chinese pedigrees with fatal family insomnia

Yao

et al. 2019

Prion

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Background : Fatal familial insomnia (FFI) is a rare autosomal-dominant inherited prion disease characterized clinically by severe sleep disorder, motor signs, dysautonomia and abnormal behaviour. FFI is caused by a missense mutation at codon 178 of the prion protein gene (PRNP). Our study is aimed to explore typical clinical and genetic features of two Chinese pedigrees with FFI and review the related literatures. Methods : Two FFI cases with family histories were recruited in our study. The main clinical features, genetic features and possible pathophysiologic mechanisms of these two FFI cases were analysed. Results : The foremost symptoms seemed to be sleep disturbances and psychosis. Progressive sympathetic symptoms, movement disturbances and memory loss were frequently observed as well. Electroencephalography (EEG) showed a minor slowing without periodic triphasic waves. Polysomnography (PSG) showed reduction in total sleep time and disturbance of sleep-related respiratory. Brain magnetic resonance imaging (MRI) did not reveal obvious abnormality. Genetic analysis disclosed the prion protein gene mutation at codon 178 (D178N), with methionine (Met) homozygosity at the polymorphic position 129 (Met129Met). Conclusions : The major clinical features of Chinese FFI are sleep dysfunction, psychiatric symptoms and sympathetic symptoms. Our patients have similar clinical characteristics as that of the typical FFI cases.

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Section: Discussionsupporting

confidence: 77%

Clinical features and genetic characteristics of two Chinese pedigrees with fatal family insomnia

Yao

et al. 2019

Prion

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“…insomnia and valine with familial CJD, 2 although this association may not be universal. 33,34 In our cohort, 28 patients could be unambiguously identified as D178N_cis129M and 5 patients as D178N_cis129V. No differences in mean antibody reactivity were seen between those 2 groups (table 4).…”

Section: Description Of the Cohortmentioning

confidence: 59%

Autoantibodies against the prion protein in individuals with PRNP mutations

Frontzek

Carta

Losa³

et al. 2020

Neurology

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ObjectiveTo determine whether naturally occurring autoantibodies against the prion protein are present in individuals with genetic prion disease mutations and controls, and if so, whether they are protective against prion disease.MethodsIn this case–control study, we collected 124 blood samples from individuals with a variety of pathogenic PRNP mutations and 78 control individuals with a positive family history of genetic prion disease but lacking disease-associated PRNP mutations. Antibody reactivity was measured using an indirect ELISA for the detection of human immunoglobulin G1–4 antibodies against wild-type human prion protein. Multivariate linear regression models were constructed to analyze differences in autoantibody reactivity between (1) PRNP mutation carriers vs controls and (2) asymptomatic vs symptomatic PRNP mutation carriers. Robustness of results was examined in matched cohorts.ResultsWe found that antibody reactivity was present in a subset of both PRNP mutation carriers and controls. Autoantibody levels were not influenced by PRNP mutation status or clinical manifestation of prion disease. Post hoc analyses showed anti-PrPC autoantibody titers to be independent of personal history of autoimmune disease and other immunologic disorders, as well as PRNP codon 129 polymorphism.ConclusionsPathogenic PRNP variants do not notably stimulate antibody-mediated anti-PrPC immunity. Anti-PrPC immunoglobulin G autoantibodies are not associated with the onset of prion disease. The presence of anti-PrPC autoantibodies in the general population without any disease-specific association suggests that relatively high titers of naturally occurring antibodies are well-tolerated.Clinicaltrials.gov identifierNCT02837705.

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“…Within 6 acquired brain autopsy, 1 neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; the remaining 5, the histopathology was typical of FFI. Harder et al,1999 [ 9 ] German 7 patients with D178N, including 5 patients with 129M/M,2 patients with 129M/V 7 genetic diagnosis of FFI, but clinical diagnosis with CJD, FFI, AD, GSS,etc Taniwaki et al,2000 [ 10 ] A Japanese family 3 patients with D178N-129M 3 patients with cerebral ataxia without overt insomnia diagnosed fCJD Dauvilliers et al,2004 [ 22 ] French 1 patient with D178N-129M/M FFI presented with circadian rhythms changes Spacey et al,2004 [ 23 ] A family of Chinese descent 1 patient with D178N-129M/M, 1 patietn genotype unclear 2 patients from this kindred were FFI Zarranz et al,2005 [ 12 ] Spanish (Basque born families) 17 patients carrying D178N-129M 7 out of 17 patients has CJD phenotype Synofzik et al,2009 [ 17 ] A German family all with D178N but 129 codon was not all clear demonstrated 1GSS with D178N-M129V, 2 CJD, 1 FFI, 1 atypical Alzheimer, 1 Freidreich ataxia, 1 brain degeneration, 1 brain softening, 1 asymptomatic member with D178N-129M Saitoh et al,2010 [ 24 ] Japanese 2 patients with D178N-129M/M 1 CJD(D178N-129M/M) phenotype and 1 FFI phenotype(D178N-129M/M) with the same PrP sc ratio glycoform Lin et al,2015 [ 7 ] Chinese 1 patient with D178N-129M 1 CJD phenotype Megelin et al,2017 [ 25 ] A French family …”

Section: Discussionmentioning

confidence: 99%

“…Taniwaki et al,2000 [10] A Japanese family 3 patients with D178N-129M 3 patients with cerebral ataxia without overt insomnia diagnosed fCJD Dauvilliers et al,2004 [22] French 1 patient with D178N-129M/M FFI presented with circadian rhythms changes Spacey et al,2004 [23] A [24] Japanese 2 patients with D178N-129M/M 1 CJD(D178N-129M/M) phenotype and 1 FFI phenotype (D178N-129M/M) with the same PrP sc ratio glycoform Lin et al,2015 [7] Chinese 1 patient with D178N-129M 1 CJD phenotype Megelin et al,2017 [25] A French family…”

Section: All Patients Presented With Ffimentioning

confidence: 99%

“…Over 60 PRNP gene mutations have been reported for genetic CJD, including missense, deletion, insertion and amber mutations [1], in which E219K and E200K are mostly highlighted [4]. D178N, a missense mutation on codon 178 of PRNP (D178N) with the substitute of asparagine for aspartic acid, has been associated with the clinicopathological phenotype of either CJD or fatal familial insomnia (FFI) depending on the polymorphic change of the prion protein (PrP) at position 129 (D178N-129M/M is related to FFI while D178N-129 V/V related to CJD) [5][6][7][8][9]. Here, we report a patient with D178N-129M/M genotype clinically manifesting corticobasal manifestations of CJD.…”

Section: Introductionmentioning

confidence: 99%

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Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N-homozygous 129M genotype

Huang

Morales

et al. 2020

Prion

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Creutzfeldt-Jakob disease (CJD) is a prion disease, usually presented with memory loss, ataxia, dementia, myoclonus, involuntary movements and psychiatric problems. D178N-homozygous 129M genotype has been recognized in the diagnosis of fatal familial insomnia (FFI) globally. Here we report a patient presented with progressive left upper limb stiffness, bradykinesia, hypomimia and weight loss (10 kg) initially. She progressed to dementia, dysphasia, dysphonia and be bedridden quickly but did not present insomnia. She was diagnosed with CJD corticobasal subtype carrying a classic D178N-129M mutation of PRNP in FFI. Remarkably, she has a strong family history of neurological degeneration diseases but the other members of this pedigree who do not carry D178N-homozygous 129M mutation in PRNP do not present any CJD or FFI symptoms. We conclude that this patient carrying D178N-homozygous 129M mutation in PRNP should be diagnosed as CJD. Thus, the clinicopathology should be considered as a crucial evidence in diagnosing some cases, but FFI could be evaluated as a differential diagnosis with a unique clinical profile.

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Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene

Abstract: (2015) Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene, Prion, 9:3, 228-235, DOI: 10.1080/19336896.2015

Cited by 13 publications

References 17 publications

Clinical features and genetic characteristics of two Chinese pedigrees with fatal family insomnia

Clinical features and genetic characteristics of two Chinese pedigrees with fatal family insomnia

Autoantibodies against the prion protein in individuals with PRNP mutations

Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N-homozygous 129M genotype

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