Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype Correlations of Ataxia With Oculomotor Apraxia Type 1.

Importance: Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia due to mutations in the aprataxin gene (APTX) that is characterized by early-onset cerebellar ataxia, oculomotor apraxia, axonal motor neuropathy, and eventual decrease of albumin serum levels.

Objectives: To improve the clinical, biomarker, and molecular delineation of AOA1 and provide genotype-phenotype correlations.

Design, Setting, And Participants: This retrospective analysis included the clinical, biological (especially regarding biomarkers of the disease), electrophysiologic, imaging, and molecular data of all patients consecutively diagnosed with AOA1 in a single genetics laboratory from January 1, 2002, through December 31, 2014.

Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism.

Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries.

Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2.

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.