TY - JOUR
T1 - Familial early onset Parkinson's disease caused by a homozygous frameshift variant in PARK7
T2 - Clinical features and literature update
AU - Stephenson, Sarah EM
AU - Djaldetti, Ruth
AU - Rafehi, Haloom
AU - Wilson, Gabrielle R.
AU - Gillies, G.
AU - Bahlo, Melanie
AU - Lockhart, Paul J.
N1 - Publisher Copyright:
© 2019
PY - 2019/7
Y1 - 2019/7
N2 - Background: Bi-allelic mutations in PARK7 are a rare cause of autosomal recessive early onset Parkinson's disease (EO-PD). To date, 30 individuals harbouring 20 unique causative variants have been described. Understanding of the spectrum of clinical features and natural history of PARK7 mediated EO-PD remain limited. Methods: We studied a family with three offspring, two of whom were affected with EO-PD. Family members underwent detailed clinical examination and DNA samples from both affected individuals and parents were analysed by exome sequencing. Results: Two brothers of Iranian descent presented at age 29 years with Parkinsonism associated with high-pitched voice and hypomimia. The brothers were followed over a six and fifteen-year period and displayed typical levodopa responsive slowly-progressive Parkinsonism. A novel homozygous frameshift mutation in PARK7 [NM_007262.4:c.90dupG, p(Ile31Aspfs*2)] was identified. Conclusions: Here we report the clinical presentation and progression of EO-PD in brothers with a novel pathogenic PARK7 variant. We expand the clinical phenotype and provide an update of clinical and pathological features of the disorder.
AB - Background: Bi-allelic mutations in PARK7 are a rare cause of autosomal recessive early onset Parkinson's disease (EO-PD). To date, 30 individuals harbouring 20 unique causative variants have been described. Understanding of the spectrum of clinical features and natural history of PARK7 mediated EO-PD remain limited. Methods: We studied a family with three offspring, two of whom were affected with EO-PD. Family members underwent detailed clinical examination and DNA samples from both affected individuals and parents were analysed by exome sequencing. Results: Two brothers of Iranian descent presented at age 29 years with Parkinsonism associated with high-pitched voice and hypomimia. The brothers were followed over a six and fifteen-year period and displayed typical levodopa responsive slowly-progressive Parkinsonism. A novel homozygous frameshift mutation in PARK7 [NM_007262.4:c.90dupG, p(Ile31Aspfs*2)] was identified. Conclusions: Here we report the clinical presentation and progression of EO-PD in brothers with a novel pathogenic PARK7 variant. We expand the clinical phenotype and provide an update of clinical and pathological features of the disorder.
KW - Clinical features
KW - DJ-1
KW - Early onset Parkinson's disease
KW - PARK7
KW - Pathology
UR - http://www.scopus.com/inward/record.url?scp=85063385211&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2019.03.013
DO - 10.1016/j.parkreldis.2019.03.013
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C2 - 30928208
AN - SCOPUS:85063385211
SN - 1353-8020
VL - 64
SP - 308
EP - 311
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -