Defective mitochondrial mRNA maturation is associated with spastic ataxia

Andrew H Crosby, Heema Patel, Barry A Chioza, Christos Proukakis, Kay Gurtz, Michael A Patton, Reza Sharifi, Gaurav Harlalka, Michael A Simpson, Katherine Dick, Johanna A Reed, Ali Al-Memar, Zofia M A Chrzanowska-Lightowlers, Harold E Cross, Robert N Lightowlers

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)


In human mitochondria, polyadenylation of mRNA, undertaken by the nuclear-encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression. Our molecular investigation of an autosomal-recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype. When subjected to poly(A) tail-length assays, mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails. Although defective mitochondrial DNA maintenance underlies a well-described group of clinical disorders, our findings reveal a defect of mitochondrial mRNA maturation associated with human disease and imply that this disease mechanism should be considered in other complex neurodegenerative disorders.
Original languageEnglish
Pages (from-to)655-60
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number5
Publication statusPublished - 12 Nov 2010


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