| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20p13 | Spongiform encephalopathy with neuropsychiatric features | 606688 | Autosomal dominant | 3 | PRNP | 176640 |
A number sign (#) is used with this entry because of evidence that spongiform encephalopathy with neuropsychiatric features is caused by heterozygous mutation in the PRNP gene (176640) on chromosome 20p13.
Nitrini et al. (1997) studied a Brazilian family in which 9 members had clinically demonstrated prion disease characterized by autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The mean age at onset was 44.8 +/- 3.8 years, and the mean duration of symptoms was 4.2 +/- 2.4 years. The dementia was characterized clinically by frontotemporal features, including early personality changes. Four patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, and 6 had parkinsonian symptoms. No periodic activity was seen in electroencephalograms in 7 patients. Pathologic evaluation of 3 patients showed severe spongiform change, neuronal loss, and minimal gliosis in the most severely affected areas. PRNP immunostaining was restricted to cerebellum and putamen.
Samaia et al. (1997) reported a family in which several members had prion encephalopathy with neuropsychiatric features. The proband had persecutory delusions, auditory hallucinations, severe depression, and a history of suicide attempts and violent behavior over a 10-year period. Neurologic symptoms such as ataxia or dementia, typical of known prion diseases, were absent. Of the other members of the patient's family identified as mutation carriers, the patient's mother had dementia and urinary incontinence and a 35-year history of similar psychiatric symptoms. The patient's uncle presented 7 years previously with abnormal behavior, including apathy, social withdrawal, mutism, and occasional violence, and subsequently developed urinary and fecal incontinence, walking difficulty, and dementia. Two sibs with the mutation had a psychiatric history of alternating severe depression and aggressiveness and 1 of them also had persecutory delusions and auditory hallucinations, whereas the third sib carrying the mutation was symptom-free. No neuropathologic findings were reported.
Hall et al. (2005) reported a family with early-onset dementia (range, 20-44 years), cerebellar signs, and extrapyramidal signs. Four patients developed neuropsychiatric symptoms in childhood or adolescence, including kleptomania, pyromania, and impulsivity. Neuropathologic examination of 4 patients showed moderate to severe cerebral atrophy, without other distinctive features. All affected individuals had a mutation in the PRNP gene.
Rogaeva et al. (2006) reported 3 affected members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by dementia, motor decline, and ataxia, resulting from a PRNP mutation. The proband showed anxiety and paranoia at age 13, developing dysarthria, gait difficulties, and trouble with self-care soon after onset. At the time of examination at age 15 years, the proband was anarthric, dysphagic, made few purposeful movements, and required total care. The proband's affected mother and affected maternal uncle had rapidly progressive dementia and motor dysfunction, but lacked psychiatric disturbance. Family history indicated at least 3 additional members with disease and a mean age at onset of 36 years (range 13 to 41).
The transmission pattern of spongiform encephalopathy with neuropsychiatric features in the families reported by Nitrini et al. (1997) and Samaia et al. (1997) was consistent with autosomal dominant inheritance.
In a Brazilian family with spongiform encephalopathy with neuropsychiatric features, Nitrini et al. (1997) identified a heterozygous mutation in the PRNP gene (176640.0022) in the proband and his affected mother.
In affected members of a family with prion encephalopathy with neuropsychiatric features, Samaia et al. (1997) identified a heterozygous mutation in the PRNP gene (N171S; 176640.0018). The mutant allele also had the val129 (176640.0005) polymorphism. The same genotype was found in 5 of 11 living relatives of the patient; only 1 mutation carrier was asymptomatic.
In 3 affected members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by personality changes, dementia, and motor decline, Rogaeva et al. (2006) identified heterozygosity for a mutation in the PRNP gene (176640.0025). The mother and uncle were homozygous for 129met (176640.0005), whereas the proband was heterozygous for 129met/val.
Hall, D. A., Leehey, M. A., Filley, C. M., Steinbart, E., Montine, T., Schellenberg, G. D., Bosque, P., Nixon, R., Bird, T. PRNP H187R mutation associated with neuropsychiatric disorders in childhood and dementia. Neurology 64: 1304-1306, 2005. [PubMed: 15824374] [Full Text: https://doi.org/10.1212/01.WNL.0000156911.70131.06]
Nitrini, R., Rosemberg, S., Passos-Bueno, M. R., da Silva, L. S. T., Iughetti, P., Papadopoulos, M., Carrilho, P. M., Caramelli, P., Albrecht, S., Zatz, M., LeBlanc, A. Familial spongiform encephalopathy associated with a novel prion protein gene mutation. Ann. Neurol. 42: 138-146, 1997. [PubMed: 9266722] [Full Text: https://doi.org/10.1002/ana.410420203]
Rogaeva, E., Zadikoff, C., Ponesse, J., Schmitt-Ulms, G., Kawarai, T., Sato, C., Salehi-Rad, S., St. George-Hyslop, P., Lang, A. E. Childhood onset in familial prion disease with a novel mutation in the PRNP gene. Arch. Neurol. 63: 1016-1021, 2006. [PubMed: 16831973] [Full Text: https://doi.org/10.1001/archneur.63.7.1016]
Samaia, H. B., Mari, J. J., Vallada, H. P., Moura, R. P., Simpson, A. J. G., Brentani, R. R. A prion-linked psychiatric disorder. (Letter) Nature 390: 241 only, 1997. [PubMed: 9384372] [Full Text: https://doi.org/10.1038/36757]