Analysis of 12 Chinese Patients with Proline-to-Leucine Mutation at Codon 102-Associated Gerstmann-Sträussler-Scheinker Disease

Abstract

Background and Purpose Gerstmann-Sträussler-Scheinker disease (GSS) with a proline-to-leucine mutation at codon 102 (P102L) in the PRNP gene is the most frequently reported GSS subtype worldwide. This study aimed to determine the epidemiological, clinical, genetic, and laboratory characteristics of 12 Chinese patients with P102L-associated GSS (henceforth P102L GSS). Methods The enrolled P102L GSS cases were analyzed according to the diagnostic criteria for Creutzfeldt-Jakob disease (CJD) issued by the China National Health Commission. Results The median onset age was 50 years (range 34 to 67 years) and sex ratio was 1:2 (males:females). Most patients displayed more than one foremost symptom. Movement symptoms were frequently reported (9 of the 12 cases), followed by rapidly progressing dementia (7 cases), mental problems (5 cases), and slowly progressing dementia (2 cases). Almost all cases displayed more sporadic CJD (sCJD)-associated neurological symptoms and signs as time progressed. Five (45.5%) of 11 cases were cerebrospinal fluid 14-3-3 positive, and 2 (25%) of 8 cases exhibited periodic sharp wave complexes in electroencephalograms. MRI abnormalities were detected in all 11 of the scanned patients. Methionine homozygous genotype at codon 129 (M129M) and glutamic acid homozygous at codon 219 (E219E) homozygosity was present in 11 cases, while 1 case was M129M homozygous and glutamic acid/lysine heterozygous at codon 219 (E219K) heterozygous. Ten of the 12 cases recalled a disease-related family history during the clinical interviews. The median survival from symptom onset of the seven dead cases was 16 months (range 10 to 44 months). Patients showing the sCJD phenotype (rapidly progressing dementia) appeared to be associated with a shorter survival time. Conclusions The indistinguishable clinical features of P102L GSS patients with sCJD, especially in the early stage, support the importance of PRNP testing for diagnosing GSS.

<p>Incidence of and Mortality Due to Human Prion Diseases in Taiwan: A Prospective 20-Year Nationwide Surveillance Study from 1998 to 2017</p>

“…[9][10][11] Long-term survivors have been reported to have either sCJD or vCJD. 9,[12][13][14] The aims of this prospective study are (1) to report all forms of human prion diseases identified in Taiwan; (2) to calculate the temporal trends in incidence by gender and age; and (3) to assess the mortality rate and disease duration.…”

Accumulation Area of a Japanese PRNP P102L Variant Associated With Gerstmann-Sträussler-Scheinker Disease: The Ariake PRNP P102L Variant

“…The survival time for PRNP P102L variant patients has varied among several reports ( Table 2 ). The median survival times in previous studies were as follows: China (12 cases), 6 months 16 ; Czech Republic (7 cases), 28 months 9 ; Germany (9 cases), 68 months 14 ; and Ariake PRNP P102L variant, 63 months. The disease duration did not differ significantly between the Ariake PRNP P102L variant and German cases (65±23 vs. 65±26 months).…”

“…In contrast, the disease duration was shorter for female patients and those who were younger at onset in Chinese cases. 16 Further research is needed to clarify the mechanisms underlying the differences in these tendencies between geographical areas.…”

A novel PRNP -G131R variant associated with familial prion disease

“…However, the clinical phenotype of GSS can be quite variable and although DWI imaging is typically negative in GSS, rare cases report a positive MRI. 6 DWI imaging associated with the PRNP-G131V/129M variant was not reported, leaving that question open. Thus, the question of whether the PRNP-G131R/ 129V variant predisposes PrP to misfold into a CJD-determining conformation rather than the GSS conformation induced by PRNP-G131V/129M will remain unanswered until the availability of direct histologic evidence.…”