Early-Onset Hereditary Alzheimer’s Disease Caused by p.M139V Mutation in the PSEN1 Gene – a Case ReportAlzheimerova demence je nejčastější demence u pacientů ve starším věku. V některých rodinách může být geneticky podmíněna. Naše kazuistika ukazuje případ 43letého muže, v jehož rodině se vyskytlo dalších šest členů rodiny s manifestací demence ve věku 40–50 let. Genetickým vyšetřením byla u pacienta prokázána patogenní mutace c.415A>G (p.M139V) v exonu 5 genu PSEN1 v heterozygotním stavu. Stejná mutace byla zjištěna u demencí postiženého bratrance. V rodině tak byla potvrzena hereditární predispozice k časné formě Alzheimerovy demence s autozomálně dominantní dědičností na molekulární úrovni. Vývoj onemocnění byl u pacienta sledován po dobu osmi let. Postupně dochází k deterioraci kognitivních funkcí a vývoji atrofických změn mozku dle magnetické rezonance. Obdobné změny jsou pozorovány u jeho bratrance. Genetické vyšetřování v rodinách zasažených demencí může být do budoucna důležité především pro možnost včasné léčby pacientů v riziku.

Česká verzia

Authors: P. Bártová ¹; S. Walczysková ²; P. Plevová ²; L. Ratajová ³; J. Havelka ⁴; E. Šilhánová ²; P. Ressner ¹; D. Školoudík ^1,5
Authors place of work: Neurologická klinika OU a FN Ostrava ¹; Oddělení lékařské genetiky, OU a FN Ostrava ²; Neurologická ambulance, Mladá Boleslav ³; Radiodiagnostické oddělení, OU a FN Ostrava ⁴; Neurologická klinika LF UP a FN Olomouc ⁵
Published in the journal: Cesk Slov Neurol N 2011; 74/107(5): 569-574
Category: Case Report

Summary

Alzheimer’s disease is the most frequently diagnosed form of dementia in older patients. In some families, a tendency to this disorder may be inherited. This case report describes a 43-year-old man in the family of whom are six other members suffering from dementia, between the ages of 40 and 50 years. Molecular genetic analysis revealed a pathogenic c.415A>G (p.M139V) mutation in exon 5 of the PSEN1 gene in the heterozygous state. The same mutation was found in a cousin who has also suffered from dementia since the age of 45. Thus a hereditary predisposition to the early-onset form of Alzheimer’s disease was confirmed in this family at a molecular level. The patient was followed up for eight years. Gradual deterioration of cognitive functions and progression of brain atrophy was observed on MRI. Similar changes were observed in the cousin. Genetic testing in families suffering from dementia may be important in the future, together with the development of drugs capable of preventing the disease.

Key words:
Alzheimer’s dementia – hereditary disease – the PSEN1 gene – gene mutation

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