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Letter

An ~140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival

¹Laboratory of Comparative Medical Genetics, Department of Microbiology & Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA; ²Laboratory of Genomic Diversity, National Cancer Institute–Frederick, Frederick, Maryland 21702, USA; ³Institute of Human Genetics, Institute of Genetics, and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; ⁴National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20894, USA; ⁵Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA; ⁶Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA

The leading genetic cause of infant mortality is spinal muscular atrophy (SMA), a clinically and genetically heterogeneous group of disorders. Previously we described a domestic cat model of autosomal recessive, juvenile-onset SMA similar to human SMA type III. Here we report results of a whole-genome scan for linkage in the feline SMA pedigree using recently developed species-specific and comparative mapping resources. We identified a novel SMA gene candidate, LIX1, in an ~140-kb deletion on feline chromosome A1q in a region of conserved synteny to human chromosome 5q15. Though LIX1 function is unknown, the predicted secondary structure is compatible with a role in RNA metabolism. LIX1 expression is largely restricted to the central nervous system, primarily in spinal motor neurons, thus offering explanation of the tissue restriction of pathology in feline SMA. An exon sequence screen of 25 human SMA cases, not otherwise explicable by mutations at the SMN1 locus, failed to identify comparable LIX1 mutations. Nonetheless, a LIX1-associated etiology in feline SMA implicates a previously undetected mechanism of motor neuron maintenance and mandates consideration of LIX1 as a candidate gene in human SMA when SMN1 mutations are not found.

⁸ Corresponding author.

E-mail fyfe{at}cvm.msu.edu; fax (517) 353-8957.

Supplemental material is available online at www.genome.org. The sequence data from this study has been submitted to GenBank under accession no. DQ250154.

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5268806.

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