Evidence for synergistic effects of PRNP and ATP7B mutations in severe neuropsychiatric deterioration

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• 作者：Nauzer Forbes ; Susan Goodwin ; Kevin Woodward ; David G Morgan…
• 关键词：Wilson’s disease ; Prion disease ; Copper ; ATP7B ; PRNP ; Prion protein ; PrP ; Synergistic mutations ; Movement disorder
• 刊名：BMC Medical Genetics
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：332 KB
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• 刊物主题：Human Genetics; Genetics and Population Dynamics;
• 出版者：BioMed Central
• ISSN：1471-2350

文摘

Background Wilson’s disease (WD), a rare cause of neuropsychiatric deterioration, is associated with mutations in the ATP7B gene. Prion diseases are also rare causes of neuropsychiatric deterioration that can occur sporadically without an identifiable cause, or can be attributed to mutations in the PRNP gene. Case presentation Here we describe a biological “experiment of nature-in which a patient presented with severe neuropsychiatric decline and strong biochemical evidence of WD. Genetic analysis revealed that he was a compound heterozygote for two ATP7B sequence variants (c.2165dupT, p.Arg723Glufs*32; and c.4039G-?A, p.Gly1347Ser), the first having been reported once previously, and the second being novel. In addition, the patient was heterozygous for a PRNP variant, c.160G-?A, p.Gly54Ser, that has been reported in a neuropsychiatric patient only once previously in association with a similarly severe clinical course of neuropsychiatric disease and early age of onset, but no accompanying information on ATP7B genotype. Of particular interest was the observation that the patient’s older sister, who carried the same ATP7B genotype and laboratory evidence for biochemical WD but was clinically asymptomatic, lacked the PRNP variant allele. Conclusions We propose that synergism may occur between at least some allelic variants of ATP7B and PRNP, possibly exerted through effects on cellular copper metabolism.