Cerebellum (2009) 8:448–453 Laboratory studies were notable for elevated alpha- fetoprotein (7.8 ng/mL, normal less than 6.7 ng/mL). Normal studies included serum electrolytes, renal function testing, liver function testing, vitamin B12, folate, homocysteine, methylmalonic acid, copper, ceruloplasmin, creatinine kinase, thyroid function studies, serum protein electropho- resis with immunofixation, erythrocyte sedimentation rate, antinuclear antibodies, and tests for GAD-65, thyroglobulin, gliadin, and Yo autoantibodies. Rapid plasma reagin and HTLV I/II screening were nonreactive. A sensorimotor neuropathy autoantibody panel (Athena Diagnostics, Inc.) was negative. Previous tests for follicle-stimulating hor- mone, luteinizing hormone, prolactin, estradiol, progester- one, testosterone, and cortisol were normal. Magnetic resonance imaging showed cerebellar atrophy. A nerve conduction study showed a sensorimotor axonal neuropathy. Echocardiogram was normal. The family is from Pakistan, and consanguinity was reported (Fig. 1), but there were no other individuals in the family identified with ataxia. Genetic testing included normal sequencing of the aprataxin gene (APTX) and the alpha-tocopherol transfer 449 protein gene (TTPA). No repeat expansions were detected in the frataxin gene (FXN). Sequencing of the senataxin gene revealed a homozygous insertion of a thymidine at position +2 of intron 16 (IVS16 + 2insT; Fig. 1). Materials and Methods Genomic DNA was prepared from blood using Autopure LS (Qiagen) according to the manufacturer’s instructions. Sequencing of senataxin coding exons and the neighboring intronic regions was performed from genomic DNA using a 3730 DNA Analyzer (Applied Biosystems). Primer sequen- ces utilized were as described in Criscuolo et al. [5]. Total RNA from peripheral blood was extracted using the PAXgene Blood RNA Kit (Qiagen) per the manufacturer’s instructions. RNA quality control was performed using an Agilent Bioanalyzer 2100 (Agilent Technologies). Human fetal and adult brain were obtained from the NICHD Brain and Tissue Bank for Developmental Disorders (University of Maryland, Baltimore, MD, USA). Total RNA was obtained Fig. 1. A homozygous intronic point mutation in the senataxin gene in a patient with ataxia with oculomotor apraxia type 2. The pedigree of the family described in this report is shown. The affected proband is indicated by a filled circle. No other individuals were reported to have ataxia. A schematic of the senataxin exon/intron junction is shown for exon 16 with the corresponding results of DNA sequencing for the proband. Intronic sequence is denoted by a dashed underline. The identified mutation, a thy- midine insertion at position +2 of the intron, is indicated by an arrow. The consensus sequence of a 5′ splice site is shown above the patient’s sequence