Reply [to Dr. Elsayed and colleagues]
Annals of Neurology , Volume 79 - Issue 2 p. 337- 338
We thank Dr Elsayed and colleagues for their interest in our article, reporting for the first time pathogenic DNAJC6 mutations associated with autosomal recessive, early onset Parkinson disease (EOPD). Mutations in this gene had been previously reported as a cause of juvenile onset parkinsonism (YOPD; onset age < 20 years) with atypical clinical features. Elsayed and colleagues report a Sudanese patient of Yemeni origins with YOPD, caused by a novel homozygous truncating DNAJC6 mutation (c. 2365C>T, predicted protein effect: p.Gln789*). The patient developed juvenile onset (10 years old) akinetic–rigid parkinsonism that was only mildly responsive to Ldopa treatment, and complicated within a few years by pyramidal signs, cognitive decline, seizures, and visual hallucinations. Interestingly, this novel finding fits well with our proposed genotype– phenotype correlation model in patients with DNAJC6 mutations (Table): YOPD phenotypes with additional atypical features are caused by drastic mutations leading to total loss of function, whereas EOPD phenotype (older onset and absence of atypical features) are caused by milder mutations with residual protein function (as those described in our study). Thus, screening of DNAJC6 is indicated in both the patients with EOPD compatible with autosomal recessive inheritance, and those with YOPD.
|Annals of Neurology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Olgiati, S, Quadri, M, Mandemakers, W.J, & Bonifati, V. (2016). Reply [to Dr. Elsayed and colleagues]. Annals of Neurology, 79(2), 337–338. doi:10.1002/ana.24587