A family with Parkinson disease, essential tremor, bell palsy, and parkin mutations

Background: Mutations in the parkin gene cause autosomal recessive early-onset Parkinson disease (EOPD). The A265G variant in the HS1 binding protein 3 gene (HS1BP3) is common in essential tremor (ET). Objective: To investigate the presence of mutations in the parkin gene and the A265G variant in the HS1BP3 gene in a Mexican family with EOPD, ET, and Bell palsy. Design: Direct sequencing, semiquantitative polymerase chain reaction, and reverse transcription-polymerase chain reaction were performed in the 14 members of this family. Setting: Mexican family. Patients: Two patients with EOPD were analyzed. Results: Compound heterozygous mutations (EX 3_6 del and EX 5 del) in the parkin gene were identified in 2 patients with EOPD, characterized by beneficial response to levodopa, relatively slow progression, and motor complications. Although heterozygous EX 3_6 del and homozygous EX 5 del mutations in the parkin gene have been previously described, to our knowledge, this is the first report of these mutations in compound heterozygotes. Seven heterozygous A265G variants in the HS1BP3 gene were found in this pedigree, but they did not cosegregate with ET, Parkinson disease, or Bell palsy, supporting the conclusion that this variant is not associated with ET. Conclusions: Compound heterozygous parkin mutations (EX 3_6 del and EX 5 del) caused EOPD in this family, but the A265G variant in the HS1BP3 gene, previously considered to be responsible for ET, was probably not pathogenically related to the ET in this family.