10.1371/journal.pone.0018931
Cord Drögemüller
Cord
Drögemüller
Ursula Reichart
Ursula
Reichart
Torsten Seuberlich
Torsten
Seuberlich
Anna Oevermann
Anna
Oevermann
Martin Baumgartner
Martin
Baumgartner
Kathrin Kühni Boghenbor
Kathrin
Kühni Boghenbor
Michael H. Stoffel
Michael
H. Stoffel
Claudia Syring
Claudia
Syring
Mireille Meylan
Mireille
Meylan
Simone Müller
Simone
Müller
Mathias Müller
Mathias
Müller
Birgit Gredler
Birgit
Gredler
Johann Sölkner
Johann
Sölkner
Tosso Leeb
Tosso
Leeb
An Unusual Splice Defect in the Mitofusin 2 Gene (<i>MFN2</i>) Is Associated with Degenerative Axonopathy in Tyrolean Grey Cattle
Public Library of Science
2011
Tyrolean Grey Cattle Tyrolean Grey cattle
monogenic autosomal recessive inheritance
Mitofusin 2 Gene
MFN 2 transcript
SNP
CMT
Charcot-Marie-Tooth disease -2A
Unusual Splice Defect
Tyrolean Grey cattle
1.9 Mb interval
mitochondrial membrane protein
MFN 2 gene
control Tyrolean Grey cattle
exonic splice enhancer
MFN 2
CNS
MFN 2 mutations
ESE
2011-04-15 02:05:14
Dataset
https://plos.figshare.com/articles/dataset/An_Unusual_Splice_Defect_in_the_Mitofusin_2_Gene_MFN2_Is_Associated_with_Degenerative_Axonopathy_in_Tyrolean_Grey_Cattle/137514
<div><p>Tyrolean Grey cattle represent a local breed with a population size of ∼5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The <i>MFN2</i> gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by <i>MFN2</i> mutations. Therefore, we considered <i>MFN2</i> a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the <i>MFN2</i> gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant <i>MFN2</i> transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle.</p></div>