J Clin Neurol.  2019 Apr;15(2):184-190. 10.3988/jcn.2019.15.2.184.

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

• Wang J
• Xiao K
• Zhou W
• Shi Q
• Dong XP

• KMID: 2467732
• DOI: http://doi.org/10.3988/jcn.2019.15.2.184

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.

Keyword

prions; Gerstmann-Sträussler-Scheinker disease; PRNP; proline-to-leucine mutation at codon 102 mutation

MeSH Terms

Age of Onset
Asian Continental Ancestry Group*
Cerebrospinal Fluid
China
Codon*
Creutzfeldt-Jakob Syndrome
Dementia
Electroencephalography
Genotype
Glutamic Acid
Humans
Magnetic Resonance Imaging
Methionine
Phenotype
Prions
Sex Ratio
Codon
Glutamic Acid
Methionine
Prions

Figure

• 

  Fig. 1 Distribution of the onset ages of 12 Chinese P102L Gerstmann-Sträussler-Scheinker disease patients. The median onset ages overall and in the different groups are shown at the top right.

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  Fig. 2 Survival times of 12 P102L Gerstmann-Sträussler-Scheinker disease patients according to gender (males and females, A) and onset age (<50 years or ≥50 years, B).

• 

  Fig. 3 Disease-related family histories and P102L mutations in PRNP in several families. The shapes, lines, and colors are defined in the panel below the figure. P102L: proline-to-leucine mutation at codon 102.

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