Abstract
PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher–Neuhäuser syndrome. Boucher–Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher–Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher–Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient’s genomic DNA from coding exons 26–29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher–Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.
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Acknowledgments
Authors would like to thank the patient, relatives, and other participants for their contribution to this research. Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institute of Health (NIH) under Award Number R01NS079388 (CPR) and NIH K02NS073836 (RSP).
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The patient described herein has given her informed consent for this manuscript’s publication. No patient-identifying information has been included in this manuscript.
Conflicts of interest
Dr. Deik has no conflicts of interest. Ms. Johannes has no conflicts of interest. Dr. Rucker has no conflicts of interest. Dr. Sánchez has no conflict of interest. Dr. Brodie has no conflicts of interest. Dr. Deegan has no conflicts of interest. Ms. Landy has no conflicts of interest. Dr. Kajiwara has no conflict of interest. Dr. Scelsa has no conflicts of interest. Dr. Saunders-Pullman has no conflicts of interest. She is funded in part through NIH K02NS073836. Dr. Paisán-Ruiz has no conflicts of interest.
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Deik, A., Johannes, B., Rucker, J.C. et al. Compound heterozygous PNPLA6 mutations cause Boucher–Neuhäuser syndrome with late-onset ataxia. J Neurol 261, 2411–2423 (2014). https://doi.org/10.1007/s00415-014-7516-3
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DOI: https://doi.org/10.1007/s00415-014-7516-3